DNA修复基因SNPs与HCC易感关系及MIF启动子多态性对HCC预后的影响
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摘要
原发性肝癌主要为肝细胞癌(HCC)，是最常见的严重威胁人们生命健康的恶性肿瘤之一。肝癌的病死率分列我国城市和农村癌症死亡率的第二位和第一位。目前，对其可能的发病病因有了初步的了解，但其发病机制尚未完全清楚, HBV、HCV感染是引起肝细胞肝癌的最重要的原因，饮酒、吸烟、家族史均被认为是发生肝癌的重要的危险因素。
DNA修复损伤基因在维持基因遗传信息的稳定性方面具有重要作用，DNA修复通路的遗传性缺陷可能使基因的完整性遭遇破坏，使细胞向肿瘤细胞转变，DNA损伤修复基因单核苷酸多态性可以改变修复酶的结构和功能，进而影响基因的稳定性和肿瘤的发生。
XRCC1及XPD基因是修复损伤基因， XRCC1主要参与基因碱基切除修复而XPD基因主要参与基因核苷酸切除修复，这些位点单个碱基的易变引起表达蛋白功能的改变，导致肿瘤的发生。本研究对于XRCC1-194、XRCC1-280及XPD-312三位点基因多态性进行分析，以期揭示其与肝癌易感性的关系。
以甲胎蛋白为重要标志物的实验室检查结合影像技术对HCC的诊断已具备较完善的诊断体系，术前诊断与病理诊断符合率已达到97.4％。而目前关于肝癌预后主要依据术后病理分型、转移和复发等方面的指标进行判断，而这种对预后的判定往往也只有在进行外科手术、取得组织标本后方能进行。不同的肝癌患者其预后指标存在着差异性，而引起这种差异性的原因目前还知之甚少。巨噬细胞移动抑制因子(MIF)与许多肿瘤存在联系，甚至有的认为其可以作为相关肿瘤判断预后的一重要标志物。有研究表明MIF启动子基因多态性可能影响MIF的表达作用，影响肿瘤的预后。MIF启动子基因多态性与肝癌的预后是否存在关系，存在何种关系，目前尚无文献报道。
目的：
1.探讨DNA修复基因XRCC1及XPD基因多态性与HCC易感性的关系。
2.以性别、年龄、HBV感染、吸烟、饮酒和家族史为发病危险因素条件下基因多态性对肝细胞癌发病的影响，进一步阐明XRCC1-194、XRCC1-280和XPD-312三位点多态性与中国汉族人肝癌发病风险的关系。
3.分析HCC病人MIF－794启动子基因CATT微卫星多态现象与肝癌预后相关指标的联系，评价其在肝切除术预后判断的价值，期望为HCC预后判断提供可能。
研究内容及方法：
1、XRCC1及XPD基因单核苷酸多态性与肝细胞癌易感关系的研究
采用以医院为基础的病例-对照研究方法。研究对象为来自同一地域的汉人群，病例组来自于2009.1-2010.12就治于大坪医院并经组织病理学确诊为HCC的患者，对照组为随机选择同一时期来自于同一地域在大坪医院进行健康体检的个体。
1.1采集调查对象外周静脉血3－5ml于含有EDTA-K2的抗凝采血管中，编号后于－20℃冰箱保存。采用Tiangen生物科技有限公司血液基因组DNA提取试剂盒，按产品操作说明书提取血液标本基因组DNA。
1.2应用限制性片段长度多态性聚合酶链反应(PCR-RFLP)技术及基因测序的方法进行基因型判定。
1.3以χ2检验分析XRCC1Arg194Trp、XRCC1Arg280His和XPD Asp312Asn位点的基因型及等位基因分布频率在病例组和对照组中分布存在差异性的情况。以优势等位基因型(野生型纯合子)作为对照进行比较分析，以非条件Logistic回归分析法计算OR及其95%CI表示单个基因型与HCC发生风险之间的关联性以及XRCC1和XPD两个基因联合作用情况下与HCC发生风险之间的关联性。
2、MIF启动子基因多态性对HCC预后的影响
用于MIF启动子分析的HCC病人为2009.1月-2011.6月就治于大坪医院肝胆外科接受外科手术并经组织病理学确诊为肝细胞肝癌的患者，研究对象为经手术切除肝癌且无肿瘤远处转移的患者。调查对象术后进行电话回访，观察时间最长为36个月，最短为6个月。每3月进行B超或CT复查，了解有无肿瘤复发及转移。实验观察指标包括患者肿瘤的TNM分期、肿瘤病理学检测进行组织学分型、观察时间内的生存时间、肿瘤复发及转移时间(包括淋巴结的肿大和转移)。
2.1采集调查对象外周静脉血3－5ml于含有EDTA-K2的抗凝采血管中，编号后于－20℃冰箱保存。采用tiangen生物科技有限公司血液基因组DNA提取试剂盒，按产品操作说明书提取血液标本基因组DNA。
2.2应用双向基因测序方法检测MIF基因启动子-794CATT微卫星重复序列，进行基因型鉴定。
3.3以ⅹ2检验分析比较5/5+5/6+6/6和7/X+8/X基因型之间肿瘤预后指标(肿瘤分化程度、TNM分期、生存率、复发及转移)，以T检验比较两组基因型平均生存时间的差异性。
以上所有统计检验均为双侧概率检验,所有数据处理均采用SPSS13.0统计软件分析，P＜0.05为相差显著。
结果：
1、XRCC1及XPD基因单核苷酸多态性与肝细胞癌易感关系的研究
1.1XRCC1194HCC组野生基因型(CC)为119例，杂合基因型(CT)为115例，突变纯合型(TT)为18例；XRCC1194健康对照组野生基因型(CC)为129例，杂合基因型(CT)为102例，突变纯合型(TT)为21例。非条件Logistic回归分析结果为OR﹦1.17，95%CI﹦(0.87-1.59)，P﹦0.42，表明XRCC1194位点突变等位基因型患肝癌的风险比野生纯合等位基因型高17％，但无统计学差异性。
1.2XRCC1280HCC组野生基因型(GG)为193例，杂合基因型(GA)为53例，突变纯合型(AA)为6例；XRCC1280健康对照组野生基因型(GG)为207例，杂合基因型(GA)为40例，突变纯合型(AA)为5例。非条件Logistic回归分析结果为OR﹦1.41，95%CI﹦(0.96-2.06)，P﹦0.15，表明XRCC1280位点突变等位基因型患肝癌的风险比野生纯合等位基因型高41％，但无统计学差异。
1.3XPD312肝癌组野生基因型(GG)为192例，杂合基因型(GA)为58例，突变纯合型(AA)为2例；XPD312健康对照组野生基因型(GG)为209例，杂合基因型(GA)为42例，突变纯合型(AA)为1例。非条件Logistic回归分析结果为:OR﹦1.56，95%CI﹦(1.51-2.37)，P﹦0.08，表明XPD312位点突变等位基因型患肝癌的风险是野生纯合等位基因型的1.56倍，但无统计学差异。
1.4年龄大于等于50岁和小于50岁、性别为危险因素分层分析，结果显示该两基因3个多态位点分别与性别、年龄不存在交互作用，P值均大于0.05。
1.5饮酒、吸烟、表面抗原携带及家族史为危险因素分层分析，结果显示：XRCC1-194Arg194Trp位点基因型的发生频率在病例组和对照组中均无显著性差别，但在暴露存在家族遗传因素条件下，XRCC1-194Trp基因型中，非条件Logistic回归分析结果为:OR﹦2.21，95%CI﹦(0.97-5.02)，P﹦0.15，HCC发生风险超过健康人的1.21倍，但P>0.05，无统计学意义。
1.6饮酒、吸烟、表面抗原携带及家族史为危险因素分层分析，结果显示：XRCC1-280His增加HCC的发生，非条件Logistic回归分析结果分别为:OR﹦1.51，95%CI﹦(0.99-2.30)，P﹦0.10；OR﹦1.38，95%CI﹦(0.88-2.18)，P﹦0.15；OR﹦1.68，95%CI﹦(1.08-2.60)，P﹦0.04；OR﹦4.20，95%CI﹦(1.34-13.20)，P﹦0.03。虽然在暴露饮酒、吸烟条件下XRCC1-280His增加HCC的发生，但P值均大于0.05,结果无统计学意义，在HBV感染因素、肝癌家族史因素下，HCC的发生比健康人群多0.68倍和3.2倍，并且P值均小于0.05。
1.7饮酒、吸烟、表面抗原携带及家族史为危险因素分层分析，结果显示：XRCC1-280His增加HCC的发生，非条件Logistic回归分析结果分别为:OR﹦1.67，95%CI﹦(1.10-2.60)，P﹦0.03；OR﹦1.87，95%CI﹦(1.18-2.96)，P﹦0.02；OR﹦1.96，95%CI﹦(1.24-3.10)，P﹦0.01；OR﹦3.40，95%CI﹦(1.32-8.76)，P﹦0.03。结果表明饮酒、吸烟、HBV感染因素、肝癌家族史四个因素均与XPD-312Asn存在交互作用，增加肝癌的发病风险，P值均小于0.05，有统计学意义。
1.8包含XRCC1194Trp＋XRCC1280His，XRCC1194Trp＋XPD312Asn和XRCC1280His＋XPD312Asn等位基因的基因型增加HCC的发生，非条件Logistic回归分析结果分别为:OR﹦1.72，95%CI﹦(1.01-2.95)，P﹦0.10；OR﹦2.00，95%CI﹦(1.14-3.38)，P﹦0.04；OR﹦3.38，95%CI﹦(1.64-6.94)，P﹦0.00。
2、MIF启动子基因多态性对HCC预后的影响
2.1本组病例男性182例、女性59例，年龄范围为21－73，平均年龄为50.1±9.3岁。包含有5/5、5/6、5/7、5/8、6/6、6/7、6/8、7/7、7/8共九种MIF－794启动子基因CATT重复序列的基因型，其结果如下：
MIF－794CATT5/5重复序列病例19例，平均生存时间20.61±7.97月，Ⅰ、Ⅱ、Ⅲ、Ⅳ期分别为6、6、4、3例，组织标本高、中、低分化分别为4、6、9例，转移复发7例，死亡5例；5/6重复序列病例32例，平均生存时间19.97±8.09月，Ⅰ、Ⅱ、Ⅲ、Ⅳ期分别为12、7、7、6例，组织标本高、中、低分化分别为4、15、13例，转移复发15例，死亡9例；5/7重复序列病例25例，平均生存时间16.16±7.36月，Ⅰ、Ⅱ、Ⅲ、Ⅳ期分别为4、7、8、6例，组织标本高、中、低分化分别为2、6、17例，转移复发14例，死亡10例；5/8重复序列病例4例，平均生存时间19.25±8.77月，Ⅰ、Ⅱ、Ⅲ、Ⅳ期分别为0、1、0、3例，组织标本高、中、低分化分别为1、0、3例，转移复发3例，死亡2例；6/6重复序列病例51例，平均生存时间18.86±7.40月，Ⅰ、Ⅱ、Ⅲ、Ⅳ期分别为18、12、13、8例，组织标本高、中、低分化分别为4、21、26例，转移复发20例，死亡11例；6/7重复序列病例58例，平均生存时间15.36±6.28月，Ⅰ、Ⅱ、Ⅲ、Ⅳ期分别为14、12、16、16例，组织标本高、中、低分化分别为2、8、48例，转移复发37例，死亡25例；6/8重复序列病例1例，生存时间21月，Ⅰ、Ⅱ、Ⅲ、Ⅳ期分别为0、0、1、0、例，组织标本高、中、低分化分别为0、0、1例，转移复发1例，死亡1例；7/7重复序列病例25例，平均生存时间15.80±7.18月，Ⅰ、Ⅱ、Ⅲ、Ⅳ期分别为8、3、7、7例，组织标本高、中、低分化分别为2、4、19，转移复发15例，死亡11例；7/8重复序列病例26例，平均生存时间14.85±6.69月，Ⅰ、Ⅱ、Ⅲ、Ⅳ期分别为6、4、7、9例，组织标本高、中、低分化分别为2、5、19，转移复发16例，死亡11例。
2.2MIF-794CATT按高重复序列和低重复序列分组进行比较分析(7/X+8/X、5/5+5/6+6/6)，分化程度、TNM分期、生存率、复发及转移、平均生存时间五个指标统计结果均存在差异性，p＜0.05,结果如下：
(7/X+8/X)重复序列病例高中分化与低分化分别为32、107，(5/5+5/6+6/6)重复序列病例高中分化与低分化分别为54、48，P=0.000；(7/X+8/X)重复序列病例(Ⅰ+Ⅱ)期与(Ⅲ+Ⅳ)期分别为59、80，(5/5+5/6+6/6)重复序列病例(Ⅰ+Ⅱ)期与(Ⅲ+Ⅳ)期分别为61、41，P=0.008；(7/X+8/X)重复序列病例死亡人数与生存人数分别为60、79，(5/5+5/6+6/6)重复序列病例死亡人数与生存人数分别为25、77，P=0.003；(7/X+8/X)重复序列病例复发及转移人数分别为86、53，(5/5+5/6+6/6)重复序列病例复发及转移人数分别为42、60，P=0.002；(7/X+8/X)重复序列病例平均生存时间为15.73±7.68月，(5/5+5/6+6/6)重复序列病例平均生存时间为19.46±7.67月，P=0.000。
结论：
1.XRCC1-280His基因型为HBV表面抗原阳性、肝癌家族史人群易患HCC的高风险基因型。
2.XPD-312Asn基因型为吸烟、饮酒、HBV阳性、有肝癌家族史人群易患肝癌高风险基因型。
3.基因XRCC1-194Trp可能不是西南地区汉族人HCC的易感基因型。
4.XRCC1-194Trp+XPD-312Asn、XRCC1-280His+XPD-312Asn两种基因型组合均能增加西南地区汉族人HCC的发生风险。
5.MIF－794CATT5-8基因启动子低重复序列(5/5+5/6+6/6)基因型HCC患者预后较好，而高重复序列(7/X+8/X)基因型HCC预后较差。
6.MIF－794CATT基因启动子微卫星重复序列多态性为HCC手术预后判断提供可能。
Dominated by hepatocellular carcinoma (HCC), primary hepatocellular carcinoma(PHC) is one of the most common malignant tumors seriously threatening people’s health.The fatality rate of HCC has ranked the second and first place in urban and rural cancermortality respectively. Currently, some preliminary understandings to the possible causeshave been obtained, but its pathogenesis is not entirely clear. HBV and HCV infections arethe most important causes of HCC, and drinking, smoking and family history are allconsidered as the important dangerous factors for the occurrence of HCC.
DNA repair damage gene plays an important role in maintaining the stability ofgenetic information. The hereditary defect of DNA repair access may damage the integrityof genes, transforming cells to tumor cells. DNA damage repair gene mononucleotidepolymorphism may change the structure and function of repair enzyme, and then affect thestability of genes and the occurrence of tumor.
XRCC1and XPD genes are repair damage genes; XRCC1is mainly engaged in genebase excision repair, while XPD gene is mainly engaged in gene nucleotide excision repair.The mutability of single base of the locus leads to the change of expression protein infunction, which causes the occurrence of tumor. The study analyzes the polymorphism threelocus genes of XRCC1-194, XRCC1-280and XPD-312, expecting to disclose itsassociation with hepatocellular carcinoma susceptibility.
So far, the diagnosis system on HCC which combines laboratory examination withalpha fetoprotein as an important marker and image technology has been developed to amature level, with a coincidence rate of pre-operative diagnosis and pathologic diagnosis of97.4%. Currently, hepatocellular carcinoma prognosis is mainly decided based on indicatorsof post-operative pathological type, transfer and recurrence, etc. And such decision can onlybe carried out after the tissue specimen is obtained after surgical operation. Differenthepatocellular carcinoma patients have different prognosis indicators. And causes for such difference are poorly understood now. Macrophage migration inhibition factor (MIF) isrelated to many tumors. Some even believe that it can be used as one important marker forrelevant tumor decision prognosis. Research indicates MIP promoter gene polymorphismmay affect the expression of MIP and the prognosis of tumor. No literature has reportedwhether MIF promoter gene polymorphism is related to the prognosis of hepatocellularcarcinoma and what the association is.
Objective:
1. Discuss the association of DNA repair gene XRCC1and XPD gene polymorphismwith HCC susceptibility.
2. With the influence of gene polymorphism on the occurrence of hepatocellularcarcinoma under the condition of gender, age, HBV infection, smoking, drinking and familyhistory as the dangerous factors for disease occurrence, further state the relationshipbetween three locus polymorphism of XRCC1-194, XRCC1-280and XPD-312and thehepatocellular carcinoma risk of Chinese Han group.
3. Analyze the association of CATT microsatellite polymorphism of MIF-794promotergene of HCC patients with relevant indicators of hepatocellular carcinoma prognosis,evaluate its value of prognosis decision after hepatectomy, and expect to provide possibilityfor HCC prognosis decision.
Research contents and methods:
1. Study on the association of XRCC1and XPD gene mononucleotide polymorphismwith hepatocellular carcinoma susceptibility.
Adopt the hospital-based case-control research method. The research object is a groupof Han people from the same region. Members of the Case Group are HCC patientsdiagnosed by histopathology who received treatment in Daping Hospital from January2009to December2010. Members of the Control Group are individuals from the same regiontaking physical examinations in Daping Hospital in the same period and selected randomly.
1.1Collect the peripheral venous blood of3-5ml of the research objects in theanti-freezing blood vessel with ACD (citric acid, sodium citrate and dextrose), and storethem in refrigerator at the temperature of－20℃after being numbered. Adopt the bloodgenome DNA extraction kit of Tiangen Bitotech Co., Ltd. and extract blood specimengenome DNA according to the product operating manual.
1.2Apply polymerase chain reaction-restricted fragment length polymorphisms(PCR-RFLP) technology and gene sequencing method to genotype decision.
1.3Check and analyze with χ2the distribution difference of genotype of XRCC1Arg194Trp, XRCC1Arg280His and XPD Asp312Asn locus and distribution frequency ofallele in the Case Group and Control Group. Carry out comparative analysis with superiorallele (homozygote of wild type) as the comparison, and with unconditional logisticregression analysis method, calculate OR and the connection between its95%CI indicatingsingle genotype and the risk HCC occurrence and the connection between it and the risk ofHCC occurrence under the joint action of XRCC1and XPD genes.
2. Influence of MIF promoter gene polymorphism on the prognosis of HCC
The HCC patient applied to MIF promoter analysis are HCC patients diagnosed byhistopathology receiving surgical operations in the Department Of Hepatobiliary Surgery ofDaping Hospital from January2009to June2011. No tumor metastasis has been observedin all research objects. Phone return visits were paid to the research objects after operations,and the observing time lasted for6to36months. B Ultrasound or CT reexamination wascarried out every3months to observe whether there is reoccurrence or transfer of tumor.Experimental observation indicators include TNM staging of patient tumor, tumorpathologic inspection for histological classification, survival time in observing time andtime of reoccurrence and transfer of tumor (including swelling and transfer of lymph node).
2.1Collect the peripheral venous blood of3-5ml of the research object in theanti-freezing blood vessel with ACD (citric acid, sodium citrate and dextrose), and storethem in refrigerator at the temperature of－20℃after being numbered. Adopt the bloodgenome DNA extraction kit of Tiangen Bitotech Co., Ltd. and extract blood specimengenome DNA according to the product operating manual.
2.2Apply bidirectional gene sequencing method to check the repeated sequence of-794CATT microsatellite of MIF gene promoter for genotype identification.
3.3Check, analyze and compare with χ2the tumor prognosis indicators (tumordifferentiation degree, TNM staging, survival rate, reoccurrence and transfer) between5/5+5/6+6/6and7/X+8/X genotypes, and check and compare with T the difference ofaverage survival time between two genotypes.
All the above statistical tests are bilateral probability test, all data processing adopts SPSS13.0statistical software for analysis, and P＜0.05is marked difference.
Results:
1. Study on the association of XRCC1and XPD gene mononucleotide polymorphismwith hepatocellular carcinoma (HCC) susceptibility
1.1XRCC1194HCC group contains119cases of wild genotype (CC),115cases ofheterozygosis genotype (CT) and18cases of TT genotype. XRCC1194healthy ControlGroup contains129cases of wild genotype (CC),102cases of heterozygosis genotype (CT)and21cases of (TT) genotype. The results of unconditioned logistic regression analysis are:OR﹦1.17,95%CI﹦(0.87-1.59), P﹦0.42, which indicate that the risk of XRCC1194locus heterozygosis allelic genotype to be attacked by liver cancer is17%higher than wildhomozygosis allelic genotype, but there is no statistic otherness.1.2XRCC1280HCCcontains193cases of wild genotype (GG),53cases of heterozygosis genotype (GA) and6cases of AA genotype. XRCC1280healthy Control Group contains207cases of wildgenotype (GG),40cases of heterozygosis genotype (GA) and5cases of (AA) genotype.The results of unconditioned logistic regression analysis are: OR﹦1.41,95%CI﹦(0.96-2.06), P﹦0.15, which indicate that the risk of XRCC1280locus heterozygosis allelicgenotype to be attacked by liver cancer is41%higher than wild homozygosis allelicgenotype, but there is no statistic otherness.1.3XPD312liver cancer group contains192cases of wild genotype (GG),58cases of heterozygosis genotype (GA) and2cases ofAA genotype. XPD312healthy Control Group contains209cases of wild genotype (GG),42cases of heterozygosis genotype (GA) and1case of (AA) genotype. The results ofunconditioned logistic regression analysis are: OR﹦1.56,95%CI﹦(1.51-2.37), P﹦0.08,which indicate that the risk of XPD312locus heterozygosis allelic genotype to be attackedby liver cancer is1.56times of wild homozygosis allelic genotype, but there is no statisticotherness.
1.4The results of stratified analysis taking age (Equal to or above50and below50)and sex as risk factors indicate that the3polymorphic loci of the two genes have nointeraction with sex and age and value P is bigger than0.05for both of them.
1.5The results of stratified analysis taking drinking, smoking, surface antigen carryingand family history as risk factors indicate that there is no obvious difference of XRCC1-194Arg194Trp locus genotype occurrence frequency in the Case Group and Control Group. But for XRCC1-194Trp genotype exposing to the condition of family genetic factor, the resultsof unconditioned logistic regression analysis are: OR﹦2.21,95%CI﹦(0.97-5.02), P﹦0.15which indicate that the risk of HCC occurrence is1.2times of the healthy people. SinceP>0.05, there is no statistic otherness.
1.6The results of stratified analysis taking drinking, smoking, surface antigen carryingand family history as risk factors indicate that XRCC1-280His increases the occurrencefrequency of HCC, and the results of unconditioned logistic regression analysis are: OR﹦1.51,95%CI﹦(0.99-2.30), P﹦0.10; OR﹦1.38,95%CI﹦(0.88-2.18), P﹦0.15; OR﹦1.68,95%CI﹦(1.08-2.60), P﹦0.04and OR﹦4.20，95%CI﹦(1.34-13.20), P﹦0.03. Althoughduring the exposure to drinking and smoking, XRCC1-280His increases the occurrencefrequency of HCC, the results have no statistic meaning for P>0.05. For people with HBVor the family history liver cancer, the occurrence frequency HCC is0.68times and3.2times of the healthy and P is smaller than0.05in both conditions.
1.7The results of stratified analysis taking drinking, smoking, surface antigen carryingand family history as risk factors indicate that XRCC1-280His increases the occurrencefrequency of HCC, and the results of unconditioned logistic regression analysis are: OR﹦1.67,95%CI﹦(1.10-2.60), P﹦0.03OR﹦1.87,95%CI﹦(1.18-2.96), P﹦0.02; OR﹦1.96,95%CI﹦(1.24-3.10), P﹦0.01and OR﹦3.40,95%CI﹦(1.32-8.76), P﹦0.03。Theseresults indicate that drinking, smoking, HBV infection factor and family history of livercancer have interaction with XPD-312Asn, and they increase the attacking risk of livercancer, but since P lower than0.05in each condition, there is no statistic meaning.
1.8Allelic genotype containing XRCC1194Trp＋XRCC1280His, XRCC1194Trp＋XPD312Asn and XRCC1280His＋XPD312Asn increase occurrence frequency of HCCand the results of unconditioned Logistic regression are: OR﹦1.72,95%CI﹦(1.01-2.95),P﹦0.10; OR﹦2.00,95%CI﹦(1.14-3.38), P﹦0.04and OR﹦3.38,95%CI﹦(1.64-6.94),P﹦0.00.
2. Influence of MIF promoter gene polymorphism on the prognosis of HCC
2.1This Case Group contains182male cases and59female cases aging from21to73,with an average age of50.1±9.3. It includes9microsatellite CATT genotypes withrepetitive sequence of5/5,5/6,5/7,5/8,6/6,6/7,6/8,7/7and7/8. The study results aredescribed as follows:
There are19cases of5/5repetitive sequence case and the average survival time is20.61±7.97months. The Phase I, II, III, and IV respectively are6,6,4and3cases. Thehigh, intermediate, and low differentiation of tissue samples respectively are4,6and9cases. The transfer-recurrence is found on7cases and5cases die. There are32cases of5/6repetitive sequence case and the average survival time is19.97±8.09months. The Phase I,II, III, and IV respectively are12,7,7and6cases. The high, intermediate, and lowdifferentiations of tissue sample respectively are4,15and13cases. The transfer-recurrenceis found on15cases and9cases die. There are25cases of5/7repetitive sequence case andthe average survival time is16.16±7.36months. The Phase I, II, III, and IV respectively are4,7,8and6cases. The high, intermediate, and low differentiations of tissue samplerespectively are2,6and17cases. The transfer-recurrence is found on14cases and10cases die. There are4cases of5/8repetitive sequence case and the average survival time is19.25±8.77months. The Phase I, II, III, and IV respectively are0,1,0and3cases. Thehigh, intermediate, and low differentiations of tissue sample respectively are1,0and3cases. The transfer-recurrence is found on3cases and2cases die.
There are51cases of6/6repetitive sequence case and the average survival time is18.86±7.40months. The Phase I, II, III, and IV respectively are18,12,13and8cases. Thehigh, intermediate, and low differentiations of tissue sample respectively are4,21and26cases. The transfer-recurrence is found on20cases and11cases die. There are20cases of6/7repetitive sequence case and the average survival time is15.36±6.28months. The PhaseI, II, III, and IV respectively are14,12,16and16cases. The high, intermediate, and lowdifferentiations of tissue sample respectively are2,8and48cases. The transfer-recurrenceis found on37cases and25cases die. There is1case of6/8repetitive sequence case andthe average survival time is21months. The Phase I, II, III, and IV respectively are0,0,1and0case. The high, intermediate, and low differentiations of tissue sample respectivelyare0,0and1case. The transfer-recurrence is found on1case and1case die.
There are25cases of7/7repetitive sequence case and the average survival time is15.80±7.18months. The Phase I, II, III, and IV respectively are8,3,7and7cases. Thehigh, intermediate, and low differentiations of tissue sample respectively are2,4and19cases. The transfer-recurrence is found on15cases and11cases die. There are26cases of7/8repetitive sequence case and the average survival time is14.85±6.69months. The Phase I, Ii, III and IV respectively are6,4,7and9cases. The high, intermediate, and lowdifferentiations of tissue sample respectively are2,5and19cases. The transfer-recurrenceis found on16cases and11cases die.
2.2Comparative analysis is carried out on MIF-794CATT by grouping it to high andlow repetitive sequence (7/X+8/X,5/5+5/6+6/6). There is otherness in the5indexes ofdifferentiation, TNM phase, survival rate, reoccurrence and transfer and average survivaltime and P is smaller than0.05. The result is as follows:
For (7/X+8/X) repetitive sequence case, its high-intermediate differentiation and lowdifferentiation respectively are32and107, while for (5/5+5/6+6/6), they respectively are54and48, and P=0.000. For (7/X+8/X) repetitive sequence case, its phase (I+II) and phase(III+IV) respectively are59and80, while or (5/5+5/6+6/6), they respectively are61and41and P=0.008. For (7/X+8/X) repetitive sequence case, its death case and survival caserespectively are60and79, while for (5/5+5/6+6/6), they respectively are25and77andP=0.003. For (7/X+8/X) repetitive sequence case, its reoccurrence case and transfer caserespectively are86and53, while for (5/5+5/6+6/6), they respectively are42and60andP=0.002. For (7/X+8/X) repetitive sequence case, its average survival time is15.73±7.68months, while for (5/5+5/6+6/6), it is19.46±7.67months and P=0.000.
Conclusion:
1. XRCC1-280His is a high risk genotype for people with positive HBV surfaceantigen or the family history of liver cancer to be attacked by liver cancer.
2. XPD-312Asn is a high risk genotype for people with the habits of smoking anddrinking, carrying HBV or with the family history of liver cancer to be attacked by livercancer.
3. Gene XRCC1-194Trp is not the susceptibility gene of liver cancer for Han peopleliving in southwestern China.
4. The combination of gene XRCC1-194Trp+XPD-312Asn and XRCC1-280His+XPD-312Asn increases the HCC occurrence risk for Han people living in southwesternChina.
5. For MIF－794CATT5-8gene promoter, the liver cancer patient with low repetitivesequence (5/5+5/6+6/6) genotype has properly good prognosis, while the patient with highrepetitive sequence (7/X+8/X) has comparative poor prognosis.
6. The microsatellite repetitive sequence polymorphism of MIF－794CATT genepromoter provides possibilities for prognosis judgment of liver cancer operation.
DNA修复损伤基因在维持基因遗传信息的稳定性方面具有重要作用，DNA修复通路的遗传性缺陷可能使基因的完整性遭遇破坏，使细胞向肿瘤细胞转变，DNA损伤修复基因单核苷酸多态性可以改变修复酶的结构和功能，进而影响基因的稳定性和肿瘤的发生。
XRCC1及XPD基因是修复损伤基因， XRCC1主要参与基因碱基切除修复而XPD基因主要参与基因核苷酸切除修复，这些位点单个碱基的易变引起表达蛋白功能的改变，导致肿瘤的发生。本研究对于XRCC1-194、XRCC1-280及XPD-312三位点基因多态性进行分析，以期揭示其与肝癌易感性的关系。
以甲胎蛋白为重要标志物的实验室检查结合影像技术对HCC的诊断已具备较完善的诊断体系，术前诊断与病理诊断符合率已达到97.4％。而目前关于肝癌预后主要依据术后病理分型、转移和复发等方面的指标进行判断，而这种对预后的判定往往也只有在进行外科手术、取得组织标本后方能进行。不同的肝癌患者其预后指标存在着差异性，而引起这种差异性的原因目前还知之甚少。巨噬细胞移动抑制因子(MIF)与许多肿瘤存在联系，甚至有的认为其可以作为相关肿瘤判断预后的一重要标志物。有研究表明MIF启动子基因多态性可能影响MIF的表达作用，影响肿瘤的预后。MIF启动子基因多态性与肝癌的预后是否存在关系，存在何种关系，目前尚无文献报道。
目的：
1.探讨DNA修复基因XRCC1及XPD基因多态性与HCC易感性的关系。
2.以性别、年龄、HBV感染、吸烟、饮酒和家族史为发病危险因素条件下基因多态性对肝细胞癌发病的影响，进一步阐明XRCC1-194、XRCC1-280和XPD-312三位点多态性与中国汉族人肝癌发病风险的关系。
3.分析HCC病人MIF－794启动子基因CATT微卫星多态现象与肝癌预后相关指标的联系，评价其在肝切除术预后判断的价值，期望为HCC预后判断提供可能。
研究内容及方法：
1、XRCC1及XPD基因单核苷酸多态性与肝细胞癌易感关系的研究
采用以医院为基础的病例-对照研究方法。研究对象为来自同一地域的汉人群，病例组来自于2009.1-2010.12就治于大坪医院并经组织病理学确诊为HCC的患者，对照组为随机选择同一时期来自于同一地域在大坪医院进行健康体检的个体。
1.1采集调查对象外周静脉血3－5ml于含有EDTA-K2的抗凝采血管中，编号后于－20℃冰箱保存。采用Tiangen生物科技有限公司血液基因组DNA提取试剂盒，按产品操作说明书提取血液标本基因组DNA。
1.2应用限制性片段长度多态性聚合酶链反应(PCR-RFLP)技术及基因测序的方法进行基因型判定。
1.3以χ2检验分析XRCC1Arg194Trp、XRCC1Arg280His和XPD Asp312Asn位点的基因型及等位基因分布频率在病例组和对照组中分布存在差异性的情况。以优势等位基因型(野生型纯合子)作为对照进行比较分析，以非条件Logistic回归分析法计算OR及其95%CI表示单个基因型与HCC发生风险之间的关联性以及XRCC1和XPD两个基因联合作用情况下与HCC发生风险之间的关联性。
2、MIF启动子基因多态性对HCC预后的影响
用于MIF启动子分析的HCC病人为2009.1月-2011.6月就治于大坪医院肝胆外科接受外科手术并经组织病理学确诊为肝细胞肝癌的患者，研究对象为经手术切除肝癌且无肿瘤远处转移的患者。调查对象术后进行电话回访，观察时间最长为36个月，最短为6个月。每3月进行B超或CT复查，了解有无肿瘤复发及转移。实验观察指标包括患者肿瘤的TNM分期、肿瘤病理学检测进行组织学分型、观察时间内的生存时间、肿瘤复发及转移时间(包括淋巴结的肿大和转移)。
2.1采集调查对象外周静脉血3－5ml于含有EDTA-K2的抗凝采血管中，编号后于－20℃冰箱保存。采用tiangen生物科技有限公司血液基因组DNA提取试剂盒，按产品操作说明书提取血液标本基因组DNA。
2.2应用双向基因测序方法检测MIF基因启动子-794CATT微卫星重复序列，进行基因型鉴定。
3.3以ⅹ2检验分析比较5/5+5/6+6/6和7/X+8/X基因型之间肿瘤预后指标(肿瘤分化程度、TNM分期、生存率、复发及转移)，以T检验比较两组基因型平均生存时间的差异性。
以上所有统计检验均为双侧概率检验,所有数据处理均采用SPSS13.0统计软件分析，P＜0.05为相差显著。
结果：
1、XRCC1及XPD基因单核苷酸多态性与肝细胞癌易感关系的研究
1.1XRCC1194HCC组野生基因型(CC)为119例，杂合基因型(CT)为115例，突变纯合型(TT)为18例；XRCC1194健康对照组野生基因型(CC)为129例，杂合基因型(CT)为102例，突变纯合型(TT)为21例。非条件Logistic回归分析结果为OR﹦1.17，95%CI﹦(0.87-1.59)，P﹦0.42，表明XRCC1194位点突变等位基因型患肝癌的风险比野生纯合等位基因型高17％，但无统计学差异性。
1.2XRCC1280HCC组野生基因型(GG)为193例，杂合基因型(GA)为53例，突变纯合型(AA)为6例；XRCC1280健康对照组野生基因型(GG)为207例，杂合基因型(GA)为40例，突变纯合型(AA)为5例。非条件Logistic回归分析结果为OR﹦1.41，95%CI﹦(0.96-2.06)，P﹦0.15，表明XRCC1280位点突变等位基因型患肝癌的风险比野生纯合等位基因型高41％，但无统计学差异。
1.3XPD312肝癌组野生基因型(GG)为192例，杂合基因型(GA)为58例，突变纯合型(AA)为2例；XPD312健康对照组野生基因型(GG)为209例，杂合基因型(GA)为42例，突变纯合型(AA)为1例。非条件Logistic回归分析结果为:OR﹦1.56，95%CI﹦(1.51-2.37)，P﹦0.08，表明XPD312位点突变等位基因型患肝癌的风险是野生纯合等位基因型的1.56倍，但无统计学差异。
1.4年龄大于等于50岁和小于50岁、性别为危险因素分层分析，结果显示该两基因3个多态位点分别与性别、年龄不存在交互作用，P值均大于0.05。
1.5饮酒、吸烟、表面抗原携带及家族史为危险因素分层分析，结果显示：XRCC1-194Arg194Trp位点基因型的发生频率在病例组和对照组中均无显著性差别，但在暴露存在家族遗传因素条件下，XRCC1-194Trp基因型中，非条件Logistic回归分析结果为:OR﹦2.21，95%CI﹦(0.97-5.02)，P﹦0.15，HCC发生风险超过健康人的1.21倍，但P>0.05，无统计学意义。
1.6饮酒、吸烟、表面抗原携带及家族史为危险因素分层分析，结果显示：XRCC1-280His增加HCC的发生，非条件Logistic回归分析结果分别为:OR﹦1.51，95%CI﹦(0.99-2.30)，P﹦0.10；OR﹦1.38，95%CI﹦(0.88-2.18)，P﹦0.15；OR﹦1.68，95%CI﹦(1.08-2.60)，P﹦0.04；OR﹦4.20，95%CI﹦(1.34-13.20)，P﹦0.03。虽然在暴露饮酒、吸烟条件下XRCC1-280His增加HCC的发生，但P值均大于0.05,结果无统计学意义，在HBV感染因素、肝癌家族史因素下，HCC的发生比健康人群多0.68倍和3.2倍，并且P值均小于0.05。
1.7饮酒、吸烟、表面抗原携带及家族史为危险因素分层分析，结果显示：XRCC1-280His增加HCC的发生，非条件Logistic回归分析结果分别为:OR﹦1.67，95%CI﹦(1.10-2.60)，P﹦0.03；OR﹦1.87，95%CI﹦(1.18-2.96)，P﹦0.02；OR﹦1.96，95%CI﹦(1.24-3.10)，P﹦0.01；OR﹦3.40，95%CI﹦(1.32-8.76)，P﹦0.03。结果表明饮酒、吸烟、HBV感染因素、肝癌家族史四个因素均与XPD-312Asn存在交互作用，增加肝癌的发病风险，P值均小于0.05，有统计学意义。
1.8包含XRCC1194Trp＋XRCC1280His，XRCC1194Trp＋XPD312Asn和XRCC1280His＋XPD312Asn等位基因的基因型增加HCC的发生，非条件Logistic回归分析结果分别为:OR﹦1.72，95%CI﹦(1.01-2.95)，P﹦0.10；OR﹦2.00，95%CI﹦(1.14-3.38)，P﹦0.04；OR﹦3.38，95%CI﹦(1.64-6.94)，P﹦0.00。
2、MIF启动子基因多态性对HCC预后的影响
2.1本组病例男性182例、女性59例，年龄范围为21－73，平均年龄为50.1±9.3岁。包含有5/5、5/6、5/7、5/8、6/6、6/7、6/8、7/7、7/8共九种MIF－794启动子基因CATT重复序列的基因型，其结果如下：
MIF－794CATT5/5重复序列病例19例，平均生存时间20.61±7.97月，Ⅰ、Ⅱ、Ⅲ、Ⅳ期分别为6、6、4、3例，组织标本高、中、低分化分别为4、6、9例，转移复发7例，死亡5例；5/6重复序列病例32例，平均生存时间19.97±8.09月，Ⅰ、Ⅱ、Ⅲ、Ⅳ期分别为12、7、7、6例，组织标本高、中、低分化分别为4、15、13例，转移复发15例，死亡9例；5/7重复序列病例25例，平均生存时间16.16±7.36月，Ⅰ、Ⅱ、Ⅲ、Ⅳ期分别为4、7、8、6例，组织标本高、中、低分化分别为2、6、17例，转移复发14例，死亡10例；5/8重复序列病例4例，平均生存时间19.25±8.77月，Ⅰ、Ⅱ、Ⅲ、Ⅳ期分别为0、1、0、3例，组织标本高、中、低分化分别为1、0、3例，转移复发3例，死亡2例；6/6重复序列病例51例，平均生存时间18.86±7.40月，Ⅰ、Ⅱ、Ⅲ、Ⅳ期分别为18、12、13、8例，组织标本高、中、低分化分别为4、21、26例，转移复发20例，死亡11例；6/7重复序列病例58例，平均生存时间15.36±6.28月，Ⅰ、Ⅱ、Ⅲ、Ⅳ期分别为14、12、16、16例，组织标本高、中、低分化分别为2、8、48例，转移复发37例，死亡25例；6/8重复序列病例1例，生存时间21月，Ⅰ、Ⅱ、Ⅲ、Ⅳ期分别为0、0、1、0、例，组织标本高、中、低分化分别为0、0、1例，转移复发1例，死亡1例；7/7重复序列病例25例，平均生存时间15.80±7.18月，Ⅰ、Ⅱ、Ⅲ、Ⅳ期分别为8、3、7、7例，组织标本高、中、低分化分别为2、4、19，转移复发15例，死亡11例；7/8重复序列病例26例，平均生存时间14.85±6.69月，Ⅰ、Ⅱ、Ⅲ、Ⅳ期分别为6、4、7、9例，组织标本高、中、低分化分别为2、5、19，转移复发16例，死亡11例。
2.2MIF-794CATT按高重复序列和低重复序列分组进行比较分析(7/X+8/X、5/5+5/6+6/6)，分化程度、TNM分期、生存率、复发及转移、平均生存时间五个指标统计结果均存在差异性，p＜0.05,结果如下：
(7/X+8/X)重复序列病例高中分化与低分化分别为32、107，(5/5+5/6+6/6)重复序列病例高中分化与低分化分别为54、48，P=0.000；(7/X+8/X)重复序列病例(Ⅰ+Ⅱ)期与(Ⅲ+Ⅳ)期分别为59、80，(5/5+5/6+6/6)重复序列病例(Ⅰ+Ⅱ)期与(Ⅲ+Ⅳ)期分别为61、41，P=0.008；(7/X+8/X)重复序列病例死亡人数与生存人数分别为60、79，(5/5+5/6+6/6)重复序列病例死亡人数与生存人数分别为25、77，P=0.003；(7/X+8/X)重复序列病例复发及转移人数分别为86、53，(5/5+5/6+6/6)重复序列病例复发及转移人数分别为42、60，P=0.002；(7/X+8/X)重复序列病例平均生存时间为15.73±7.68月，(5/5+5/6+6/6)重复序列病例平均生存时间为19.46±7.67月，P=0.000。
结论：
1.XRCC1-280His基因型为HBV表面抗原阳性、肝癌家族史人群易患HCC的高风险基因型。
2.XPD-312Asn基因型为吸烟、饮酒、HBV阳性、有肝癌家族史人群易患肝癌高风险基因型。
3.基因XRCC1-194Trp可能不是西南地区汉族人HCC的易感基因型。
4.XRCC1-194Trp+XPD-312Asn、XRCC1-280His+XPD-312Asn两种基因型组合均能增加西南地区汉族人HCC的发生风险。
5.MIF－794CATT5-8基因启动子低重复序列(5/5+5/6+6/6)基因型HCC患者预后较好，而高重复序列(7/X+8/X)基因型HCC预后较差。
6.MIF－794CATT基因启动子微卫星重复序列多态性为HCC手术预后判断提供可能。
Dominated by hepatocellular carcinoma (HCC), primary hepatocellular carcinoma(PHC) is one of the most common malignant tumors seriously threatening people’s health.The fatality rate of HCC has ranked the second and first place in urban and rural cancermortality respectively. Currently, some preliminary understandings to the possible causeshave been obtained, but its pathogenesis is not entirely clear. HBV and HCV infections arethe most important causes of HCC, and drinking, smoking and family history are allconsidered as the important dangerous factors for the occurrence of HCC.
DNA repair damage gene plays an important role in maintaining the stability ofgenetic information. The hereditary defect of DNA repair access may damage the integrityof genes, transforming cells to tumor cells. DNA damage repair gene mononucleotidepolymorphism may change the structure and function of repair enzyme, and then affect thestability of genes and the occurrence of tumor.
XRCC1and XPD genes are repair damage genes; XRCC1is mainly engaged in genebase excision repair, while XPD gene is mainly engaged in gene nucleotide excision repair.The mutability of single base of the locus leads to the change of expression protein infunction, which causes the occurrence of tumor. The study analyzes the polymorphism threelocus genes of XRCC1-194, XRCC1-280and XPD-312, expecting to disclose itsassociation with hepatocellular carcinoma susceptibility.
So far, the diagnosis system on HCC which combines laboratory examination withalpha fetoprotein as an important marker and image technology has been developed to amature level, with a coincidence rate of pre-operative diagnosis and pathologic diagnosis of97.4%. Currently, hepatocellular carcinoma prognosis is mainly decided based on indicatorsof post-operative pathological type, transfer and recurrence, etc. And such decision can onlybe carried out after the tissue specimen is obtained after surgical operation. Differenthepatocellular carcinoma patients have different prognosis indicators. And causes for such difference are poorly understood now. Macrophage migration inhibition factor (MIF) isrelated to many tumors. Some even believe that it can be used as one important marker forrelevant tumor decision prognosis. Research indicates MIP promoter gene polymorphismmay affect the expression of MIP and the prognosis of tumor. No literature has reportedwhether MIF promoter gene polymorphism is related to the prognosis of hepatocellularcarcinoma and what the association is.
Objective:
1. Discuss the association of DNA repair gene XRCC1and XPD gene polymorphismwith HCC susceptibility.
2. With the influence of gene polymorphism on the occurrence of hepatocellularcarcinoma under the condition of gender, age, HBV infection, smoking, drinking and familyhistory as the dangerous factors for disease occurrence, further state the relationshipbetween three locus polymorphism of XRCC1-194, XRCC1-280and XPD-312and thehepatocellular carcinoma risk of Chinese Han group.
3. Analyze the association of CATT microsatellite polymorphism of MIF-794promotergene of HCC patients with relevant indicators of hepatocellular carcinoma prognosis,evaluate its value of prognosis decision after hepatectomy, and expect to provide possibilityfor HCC prognosis decision.
Research contents and methods:
1. Study on the association of XRCC1and XPD gene mononucleotide polymorphismwith hepatocellular carcinoma susceptibility.
Adopt the hospital-based case-control research method. The research object is a groupof Han people from the same region. Members of the Case Group are HCC patientsdiagnosed by histopathology who received treatment in Daping Hospital from January2009to December2010. Members of the Control Group are individuals from the same regiontaking physical examinations in Daping Hospital in the same period and selected randomly.
1.1Collect the peripheral venous blood of3-5ml of the research objects in theanti-freezing blood vessel with ACD (citric acid, sodium citrate and dextrose), and storethem in refrigerator at the temperature of－20℃after being numbered. Adopt the bloodgenome DNA extraction kit of Tiangen Bitotech Co., Ltd. and extract blood specimengenome DNA according to the product operating manual.
1.2Apply polymerase chain reaction-restricted fragment length polymorphisms(PCR-RFLP) technology and gene sequencing method to genotype decision.
1.3Check and analyze with χ2the distribution difference of genotype of XRCC1Arg194Trp, XRCC1Arg280His and XPD Asp312Asn locus and distribution frequency ofallele in the Case Group and Control Group. Carry out comparative analysis with superiorallele (homozygote of wild type) as the comparison, and with unconditional logisticregression analysis method, calculate OR and the connection between its95%CI indicatingsingle genotype and the risk HCC occurrence and the connection between it and the risk ofHCC occurrence under the joint action of XRCC1and XPD genes.
2. Influence of MIF promoter gene polymorphism on the prognosis of HCC
The HCC patient applied to MIF promoter analysis are HCC patients diagnosed byhistopathology receiving surgical operations in the Department Of Hepatobiliary Surgery ofDaping Hospital from January2009to June2011. No tumor metastasis has been observedin all research objects. Phone return visits were paid to the research objects after operations,and the observing time lasted for6to36months. B Ultrasound or CT reexamination wascarried out every3months to observe whether there is reoccurrence or transfer of tumor.Experimental observation indicators include TNM staging of patient tumor, tumorpathologic inspection for histological classification, survival time in observing time andtime of reoccurrence and transfer of tumor (including swelling and transfer of lymph node).
2.1Collect the peripheral venous blood of3-5ml of the research object in theanti-freezing blood vessel with ACD (citric acid, sodium citrate and dextrose), and storethem in refrigerator at the temperature of－20℃after being numbered. Adopt the bloodgenome DNA extraction kit of Tiangen Bitotech Co., Ltd. and extract blood specimengenome DNA according to the product operating manual.
2.2Apply bidirectional gene sequencing method to check the repeated sequence of-794CATT microsatellite of MIF gene promoter for genotype identification.
3.3Check, analyze and compare with χ2the tumor prognosis indicators (tumordifferentiation degree, TNM staging, survival rate, reoccurrence and transfer) between5/5+5/6+6/6and7/X+8/X genotypes, and check and compare with T the difference ofaverage survival time between two genotypes.
All the above statistical tests are bilateral probability test, all data processing adopts SPSS13.0statistical software for analysis, and P＜0.05is marked difference.
Results:
1. Study on the association of XRCC1and XPD gene mononucleotide polymorphismwith hepatocellular carcinoma (HCC) susceptibility
1.1XRCC1194HCC group contains119cases of wild genotype (CC),115cases ofheterozygosis genotype (CT) and18cases of TT genotype. XRCC1194healthy ControlGroup contains129cases of wild genotype (CC),102cases of heterozygosis genotype (CT)and21cases of (TT) genotype. The results of unconditioned logistic regression analysis are:OR﹦1.17,95%CI﹦(0.87-1.59), P﹦0.42, which indicate that the risk of XRCC1194locus heterozygosis allelic genotype to be attacked by liver cancer is17%higher than wildhomozygosis allelic genotype, but there is no statistic otherness.1.2XRCC1280HCCcontains193cases of wild genotype (GG),53cases of heterozygosis genotype (GA) and6cases of AA genotype. XRCC1280healthy Control Group contains207cases of wildgenotype (GG),40cases of heterozygosis genotype (GA) and5cases of (AA) genotype.The results of unconditioned logistic regression analysis are: OR﹦1.41,95%CI﹦(0.96-2.06), P﹦0.15, which indicate that the risk of XRCC1280locus heterozygosis allelicgenotype to be attacked by liver cancer is41%higher than wild homozygosis allelicgenotype, but there is no statistic otherness.1.3XPD312liver cancer group contains192cases of wild genotype (GG),58cases of heterozygosis genotype (GA) and2cases ofAA genotype. XPD312healthy Control Group contains209cases of wild genotype (GG),42cases of heterozygosis genotype (GA) and1case of (AA) genotype. The results ofunconditioned logistic regression analysis are: OR﹦1.56,95%CI﹦(1.51-2.37), P﹦0.08,which indicate that the risk of XPD312locus heterozygosis allelic genotype to be attackedby liver cancer is1.56times of wild homozygosis allelic genotype, but there is no statisticotherness.
1.4The results of stratified analysis taking age (Equal to or above50and below50)and sex as risk factors indicate that the3polymorphic loci of the two genes have nointeraction with sex and age and value P is bigger than0.05for both of them.
1.5The results of stratified analysis taking drinking, smoking, surface antigen carryingand family history as risk factors indicate that there is no obvious difference of XRCC1-194Arg194Trp locus genotype occurrence frequency in the Case Group and Control Group. But for XRCC1-194Trp genotype exposing to the condition of family genetic factor, the resultsof unconditioned logistic regression analysis are: OR﹦2.21,95%CI﹦(0.97-5.02), P﹦0.15which indicate that the risk of HCC occurrence is1.2times of the healthy people. SinceP>0.05, there is no statistic otherness.
1.6The results of stratified analysis taking drinking, smoking, surface antigen carryingand family history as risk factors indicate that XRCC1-280His increases the occurrencefrequency of HCC, and the results of unconditioned logistic regression analysis are: OR﹦1.51,95%CI﹦(0.99-2.30), P﹦0.10; OR﹦1.38,95%CI﹦(0.88-2.18), P﹦0.15; OR﹦1.68,95%CI﹦(1.08-2.60), P﹦0.04and OR﹦4.20，95%CI﹦(1.34-13.20), P﹦0.03. Althoughduring the exposure to drinking and smoking, XRCC1-280His increases the occurrencefrequency of HCC, the results have no statistic meaning for P>0.05. For people with HBVor the family history liver cancer, the occurrence frequency HCC is0.68times and3.2times of the healthy and P is smaller than0.05in both conditions.
1.7The results of stratified analysis taking drinking, smoking, surface antigen carryingand family history as risk factors indicate that XRCC1-280His increases the occurrencefrequency of HCC, and the results of unconditioned logistic regression analysis are: OR﹦1.67,95%CI﹦(1.10-2.60), P﹦0.03OR﹦1.87,95%CI﹦(1.18-2.96), P﹦0.02; OR﹦1.96,95%CI﹦(1.24-3.10), P﹦0.01and OR﹦3.40,95%CI﹦(1.32-8.76), P﹦0.03。Theseresults indicate that drinking, smoking, HBV infection factor and family history of livercancer have interaction with XPD-312Asn, and they increase the attacking risk of livercancer, but since P lower than0.05in each condition, there is no statistic meaning.
1.8Allelic genotype containing XRCC1194Trp＋XRCC1280His, XRCC1194Trp＋XPD312Asn and XRCC1280His＋XPD312Asn increase occurrence frequency of HCCand the results of unconditioned Logistic regression are: OR﹦1.72,95%CI﹦(1.01-2.95),P﹦0.10; OR﹦2.00,95%CI﹦(1.14-3.38), P﹦0.04and OR﹦3.38,95%CI﹦(1.64-6.94),P﹦0.00.
2. Influence of MIF promoter gene polymorphism on the prognosis of HCC
2.1This Case Group contains182male cases and59female cases aging from21to73,with an average age of50.1±9.3. It includes9microsatellite CATT genotypes withrepetitive sequence of5/5,5/6,5/7,5/8,6/6,6/7,6/8,7/7and7/8. The study results aredescribed as follows:
There are19cases of5/5repetitive sequence case and the average survival time is20.61±7.97months. The Phase I, II, III, and IV respectively are6,6,4and3cases. Thehigh, intermediate, and low differentiation of tissue samples respectively are4,6and9cases. The transfer-recurrence is found on7cases and5cases die. There are32cases of5/6repetitive sequence case and the average survival time is19.97±8.09months. The Phase I,II, III, and IV respectively are12,7,7and6cases. The high, intermediate, and lowdifferentiations of tissue sample respectively are4,15and13cases. The transfer-recurrenceis found on15cases and9cases die. There are25cases of5/7repetitive sequence case andthe average survival time is16.16±7.36months. The Phase I, II, III, and IV respectively are4,7,8and6cases. The high, intermediate, and low differentiations of tissue samplerespectively are2,6and17cases. The transfer-recurrence is found on14cases and10cases die. There are4cases of5/8repetitive sequence case and the average survival time is19.25±8.77months. The Phase I, II, III, and IV respectively are0,1,0and3cases. Thehigh, intermediate, and low differentiations of tissue sample respectively are1,0and3cases. The transfer-recurrence is found on3cases and2cases die.
There are51cases of6/6repetitive sequence case and the average survival time is18.86±7.40months. The Phase I, II, III, and IV respectively are18,12,13and8cases. Thehigh, intermediate, and low differentiations of tissue sample respectively are4,21and26cases. The transfer-recurrence is found on20cases and11cases die. There are20cases of6/7repetitive sequence case and the average survival time is15.36±6.28months. The PhaseI, II, III, and IV respectively are14,12,16and16cases. The high, intermediate, and lowdifferentiations of tissue sample respectively are2,8and48cases. The transfer-recurrenceis found on37cases and25cases die. There is1case of6/8repetitive sequence case andthe average survival time is21months. The Phase I, II, III, and IV respectively are0,0,1and0case. The high, intermediate, and low differentiations of tissue sample respectivelyare0,0and1case. The transfer-recurrence is found on1case and1case die.
There are25cases of7/7repetitive sequence case and the average survival time is15.80±7.18months. The Phase I, II, III, and IV respectively are8,3,7and7cases. Thehigh, intermediate, and low differentiations of tissue sample respectively are2,4and19cases. The transfer-recurrence is found on15cases and11cases die. There are26cases of7/8repetitive sequence case and the average survival time is14.85±6.69months. The Phase I, Ii, III and IV respectively are6,4,7and9cases. The high, intermediate, and lowdifferentiations of tissue sample respectively are2,5and19cases. The transfer-recurrenceis found on16cases and11cases die.
2.2Comparative analysis is carried out on MIF-794CATT by grouping it to high andlow repetitive sequence (7/X+8/X,5/5+5/6+6/6). There is otherness in the5indexes ofdifferentiation, TNM phase, survival rate, reoccurrence and transfer and average survivaltime and P is smaller than0.05. The result is as follows:
For (7/X+8/X) repetitive sequence case, its high-intermediate differentiation and lowdifferentiation respectively are32and107, while for (5/5+5/6+6/6), they respectively are54and48, and P=0.000. For (7/X+8/X) repetitive sequence case, its phase (I+II) and phase(III+IV) respectively are59and80, while or (5/5+5/6+6/6), they respectively are61and41and P=0.008. For (7/X+8/X) repetitive sequence case, its death case and survival caserespectively are60and79, while for (5/5+5/6+6/6), they respectively are25and77andP=0.003. For (7/X+8/X) repetitive sequence case, its reoccurrence case and transfer caserespectively are86and53, while for (5/5+5/6+6/6), they respectively are42and60andP=0.002. For (7/X+8/X) repetitive sequence case, its average survival time is15.73±7.68months, while for (5/5+5/6+6/6), it is19.46±7.67months and P=0.000.
Conclusion:
1. XRCC1-280His is a high risk genotype for people with positive HBV surfaceantigen or the family history of liver cancer to be attacked by liver cancer.
2. XPD-312Asn is a high risk genotype for people with the habits of smoking anddrinking, carrying HBV or with the family history of liver cancer to be attacked by livercancer.
3. Gene XRCC1-194Trp is not the susceptibility gene of liver cancer for Han peopleliving in southwestern China.
4. The combination of gene XRCC1-194Trp+XPD-312Asn and XRCC1-280His+XPD-312Asn increases the HCC occurrence risk for Han people living in southwesternChina.
5. For MIF－794CATT5-8gene promoter, the liver cancer patient with low repetitivesequence (5/5+5/6+6/6) genotype has properly good prognosis, while the patient with highrepetitive sequence (7/X+8/X) has comparative poor prognosis.
6. The microsatellite repetitive sequence polymorphism of MIF－794CATT genepromoter provides possibilities for prognosis judgment of liver cancer operation.
引文
1. Ferlay J, Shin HR, Bray F, Forman D,Mathers CD, Parkin D.GLOBOCAN2008,Cancer Incidence and Mortality Worldwide: IARC CancerBase No.10.Lyon, France:International Agency for Research on Cancer; Year. Available at:http://globocan.iarc.fr.2010. Last accessed8/17/2010。
2. Jemal A, Bray F, Center MM, Ferlay J, et a1．Global cancer statistics. CA Cancer JClin.2011Mar-Apr;61(2):69-90.
3. Thomas MB and Zhu AX．Hepatocellular Carcinoma：The Need for progress[J]．JClin Oncol，2005，23(13)：2892-2899.
4. Kuang SY，Jackson PE，Wang JB，et al．Specific mutations of hepatitis B virus inplasma predict liver cancer development[J]．Proc Natl Acad Sci USA，2004，101(10)：3575-3580。
5. Parkin DM， Bray F， Ferlay J， et a1．Global cancer statistics，2002[J]． CACancer J Clin，2005，55(2)：74-108.
6.杨广顺，吴志全，吴孟超．原发性肝癌的规范化综合治疗[J]．中华外科杂志，2001，39(10)：742-744．
7.郑莹,李德錄,沈玉珍,向詠梅,鲍萍萍.上海市原发性肝癌流行状况和趋势分析[J].外科理论与实践，2004,(04)：292-294.
8.曾运红,谭卫仙.原发性肝癌发病主要危险因素的Meta分析〔J〕.现代预防医学,2004,31(2):172–174。
9. Ljumovic D, Diamantis I, A1egakis AK. Differential expression of matrixmetalloproteinase in viral and non2viral chronic liver diseases〔J〕. Chin Chim Acta,2004,349:203–211.
10. Catela Ivkowia T, Loncar B, Spaventi R,et al.Association of H-ras polymorphismsand susceptibility to sporadic colon cancer [J]. Int J Oncol,2009，35(5)：1169-1173.
11. Zhang Y, Jin M, Liu B, et al. Association between H-RAS T81C geneticpolymorphism and gast rointestinal cancer risk: a population based case-controlstudy in China [J]. BMC Cancer,2008,8(5):256.
12.谢锋，徐峰，黄杨卿，等．单核苷酸多态性与肝细胞癌遗传易感性．肝脏，2006，11(6)：413-415．
13. Wang DG，Fan JB，Siao CJ，et al．Large-scale identification，mapping andgenotyping of single-nucleotide polymorphisms in the human genome[J]．Science，1998，280(5366)：1077-1082。
14. Sehl M E, Langer L R, Papp J C, et al. Associations between single nucleotidepolymorphisms in double2st randed DNA repair pat hway genes and familial breastcancer [J]. Clin Cancer Res,2009,15(6):2192-2203.
15. Walsh T, King M C. Ten genes for inherited breast cancer [J].Cancer Cell,2007,11(2):103-105.
16. I. Ieiri, H. Takane, T. Hirota, K. Otsubo, S. Higuchi, Genetic polymorphisms of drugtransporters: pharmacokinetic and pharmacodynamic consequences inpharmacotherapy. Expert Opin. Drug Metab. Toxicol.2006,2;651–674.
17. E. Shikata, I. Ieiri, S. Ishiguro, H. Aono, K. Inoue, T. Koide, S. Ohgi, K.Otsubo,Association of pharmacokinetic (CYP2C9) and pharmacodynamic (factors II,VII,IX, and X; proteins S and C; and g-glutamyl carboxylase) gene variants withwarfarin sensitivity. Blood,2004,103;2630–2635.
18. J.Q. He, J. Ruan, J.E. Connett, N.R. Anthonisen, P.D. Pare′PD, A.J. Sandford,Antioxidant gene polymorphisms and susceptibility to a rapid decline in lung functionin smokers. Am. J. Respir. Crit. Care Med,2002,166;323–328.
19. Camenisch U, Naegeli H.Role of DNA repair in the protection against genotoxicstress，EXS.2009;99:111-50。
20. Eker AP, Quayle C, Chaves I, vander Horst GT.DNA repair in mammalian cells:Direct DNA damage reversal: elegant solutions for nasty problems. Cell Mol Life Sci.2009Mar;66(6):968-80.
21. Shrivastav M, De Haro LP, Nickoloff JA.Regulation of DNA double-strand breakrepair pathway choice. Cell Res.2008Jan;18(1):134-47.
22.吴孟超。中华普外科手术学杂志.2009,3,(4);691-694.
23. Mor G, Visintin I, Lai Y, Zhao H, Schwartz P, Rutherford T, et al. Serum proteinmarkers for early detection of ovarian cancer. Proceedings of the National Academyof Sciences of the United States of America.2005;102(21):7677–82.
24. Kim K, Visintin I, Alvero AB, Mor G. Development and validation of a protein-basedsignature for the detection of ovarian cancer. Clinics in Laboratory Medicine.2009;29(1):47–55.
25. De Boer JG Polymorphisms in DNA repair and environmental interactions. MutatRes，2002，509:201–210。
26. Berwick M, Vineis P.Markers of DNA repair and susceptibility to cancer in humans:an epidemiologic review. J Natl Cancer Inst，2000，92:874–897.
27. Kubota Y，Nash RA，Kltmgland A，et al．Reconstitution of DNA base excision repairwith purified human proteins：interaction between DNA polymerase beta and theXRCC1protein[J]．EMBO J，1996，15(23)：6662-6670．
28. R.J. Hung, J. Hall, P. Brennan, P. Boffetta, Genetic polymorphisms in the baseexcision repair pathway and cancer risk: a HuGE review. Am. J. Epidemiol.2005),162(10):925–942.
29. I. Laczmanska, J. Gil, P. Karpinski, A. Stembalska, J. Kozlowska, H. Busza,A.Trusewicz, K. Pesz, D. Ramsey, K. Schlade-Bartusiak, N. Blin, M.M.Sasiadek,Influence of polymorphisms in xenobiotic-metabolizing genes andDNA-repair genes on diepoxybutane-induced SCE. Environ. Mol. Mutagen.2006,47;666–673.
30. Weber C A,Salazar E P,Stewart S A,et aI. ERCC2:cDNA cloning and molecularcharacterization of a human nucleotide excision repair gene with hgh homology toyeast RAD3. EMBO J,1990,9(5):1437。
31. Shen MR, Jones IM, Mohrenweiser H. Nonconservative amino acid substitutionvariants exist at polymorphic frequency in DNA repair genes in healthy humans。Cancer Res.1998Feb15;58(4):604-8.
32. M Felicitas Lopez-Cima,1Patricia Gonzalez-Arriaga,1Laura Garcia-Castro, et aI.Polymorphisms in XPC, XPD, XRCC1, and XRCC3DNA repair genes and lungcancer risk in a population of Northern Spain. BMC Cancer.2007;7:162.
33.杨万水,高静,高姗等，吸烟与肝癌前瞻性研究的荟萃分析。肿瘤2010，30(3)：247－252。
34. Walsh B, Grant M. Public health implications of alcohol production and trade[M].Geneva: WHO,1985.
35.郝伟,杨德森,何鸣.我国饮酒现状、预测及对策[J].中国临床心理学杂志,1995,3：244－245.
36. Parkin DM,Bray F, Ferlay J. Global cancer statistics,2002〔J〕. CA Cancer J Clin,2005,55:74-108.
37.曾运红,谭卫仙.原发性肝癌发病主要危险因素的Meta分析〔J〕.现代预防医学,2004,31(2):172-174.
38. Thomp son LH, Brookman KW, Jones NJ, et al. Molecular cloning of the humanXRCC1gene, which corrects defective DNA strand break repair and sister chromaticexchange [J]. Mol Cell Biol,1990,10(12):6160-6171.
39. Thacker J,Zdzienicka MZ. The mammalian XRCC genes:their roles in DNA repairand genetic stability. DNA Repair,2003,2:655－72.
40. Richard D W. Nucleotide excision repair in mammalian cells. J Biol Chem.1997Sep19;272(38):23465-8。
41. Thornton K，Forstner M，Shen MR，et al．Purification，characterization，andcrystallization of the distal BRCT domain of the human XRCC1DNA repairprotein[J]．Protein Expr Purif，1999，16(2)：236-242．
42. Bork P，Hofmann K，Bucher P，et a1．A superfamily of conserved domains in DNAdamage-responsive cell cycle checkpoint proteins[J]．FASEB J，1997，11(1)：68-76．
43. Wilson SH．Mammalian base excision repair and DNA polymerase beta[J]．MutatRes，1998，407(3)：203-215．
44.．Kubota Y，Nash RA，Kltmgland A，et a1．Reconstitution of DNA base excisionrepair with purified human proteins：interaction between DNA polymerase beta andthe XRCC1protein[J]．EMBO J，1996，15(23)：6662-6670．
45. J.K. Horton, M. Watson, D.F. Stefanick, D.T. Shaughnessy, J.A. Taylor, S.H.Wilson,XRCC1and DNA polymerase β in cellular protection against cytotoxic DNAsingle-strand breaks. Cell Res.2008,18;48–63.
46. O.Mortusewicz, H. Leonhardt, XRCC1and PCNA are loading platforms with distinctkinetic properties and different capacities to respond to multiple DNA lesions. BMCMol. Biol.2007,8;81.
47. L.H. Thompson, M.G. West, XRCC keeps DNA from getting stranded. Mutat. Res.2000,459;1–18.
48. S. Sterpone, R. Cozzi, Influence of XRCC1genetic polymorphisms on ionizingradiation-induced DNA damage and repair. J. Nucleic Acids,2010.
49. S.Z. Abdel-Rahman, A.S. Soliman, M.L. Bondy, S. Omar, S.A. El-Badaway,H.M.Khaled, I.A. Seifeldin, B. Levin, Inheritance of the194Trp and the399Glnvariant alleles of the DNA repair gene XRCC1are associated with increased risk ofthe early-onset colorectal carcinoma in Egypt. Cancer Lett.2000,159;79–86.
50. R.J. Hung, J. Hall, P. Brennan, P. Boffetta, Genetic polymorphisms in the baseexcision repair pathway and cancer risk: a HuGE review. Am. J. Epidemiol.2005),162(10):925–942.
51. I. Laczmanska, J. Gil, P. Karpinski, A. Stembalska, J. Kozlowska, H. Busza,A.Trusewicz, K. Pesz, D. Ramsey, K. Schlade-Bartusiak, N. Blin, M.M.Sasiadek,Influence of polymorphisms in xenobiotic-metabolizing genes andDNA-repair genes on diepoxybutane-induced SCE. Environ. Mol. Mutagen.2006,47;666–673.
52. G. Ji, A. Gu, P. Zhu, Y. Xia, Y. Zhou, F. Hu, L. Song, S. Wang, X. Wang, Joint effectsof XRCC1polymorphisms and polycyclic aromatic hydrocarbons exposure on spermDNA damage and male infertility.Toxicol. Sci.,2010,116;92–98.
53. E.M. Sturgis, E.J. Castillo, L. Li, R. Zheng, A.S. Eicher, G.L. Clayman, S.S. Strom,M.R.Spitz, Q. Wei, Polymorphisms of DNA repair gene XRCC1in squamous cellcarcinoma of the head and neck. Carcinogenesis,1999,20(11):2125–2129.
54. C. Harms, S.A. Salama, C.H. Sierra-Torres, N. Cajas-Salazar, W.W. Au,Polymorphisms in DNA repair genes, chromosome aberrations and lung cancer.Environ.Mol. Mutagen.2004,44;74–82.
55. J.M. Lee, Y.C. Lee, S.Y. Yang, P.W. Yan, S.P. Luh, C.J. Lee, C.J. Chen, M.T. Wu,Genetic polymorphisms of XRCC1and risk of the esophageal cancer. Int. J. Cancer,2001,95;240–246.
56. H. Shen, Y. Xu, Y. Qian, R. Yu, Y. Qin, L. Zhou, L. Wang, X. Wang, M.R. Spitz, Q.Wei,Polymorphisms of the DNA repair gene XRCC1and risk of gastric cancer in aChinese population. Int. J. Cancer,2000,88;601–606.
57. S.Z. Abdel-Rahman, A.S. Soliman, M.L. Bondy, S. Omar, S.A. El-Badaway,H.M.Khaled, I.A. Seifeldin, B. Levin, Inheritance of the194Trp and the399Glnvariant alleles of the DNA repair gene XRCC1are associated with increased risk ofthe early-onset colorectal carcinoma in Egypt. Cancer Lett.2000,159;79–86.
58. Lunn RM, Helzlsouer KJ, Parshad R, Umbach DM, Harris EL, Sanford KK, Bell DA.XPD polymorphisms: effects on DNA repair proficiency。Carcinogenesis.2000Apr;21(4):551-5.
59. Shen MR, Jones IM, Mohrenweiser H. Nonconservative amino acid substitutionvariants exist at polymorphic frequency in DNA repair genes in healthy humans。Cancer Res.1998Feb15;58(4):604-8.
60. Jia Z, Yin Z, Guan P, Zhou B. The Association between Polymorphisms of XPD andSusceptibility of Lung Cancer: A meta Analysis. Zhongguo Fei Ai Za Zhi.2009,12(10):1079-84.
61. Yuan H, Niu YM, Wang RX, Li HZ, Chen N.Association between XPD Lys751Glnpolymorphism and risk of head and neck cancer: a meta-analysis Genet Mol Res.2011Nov22;10(4).---。
62.宋春英，谭文，林东昕．中国DNA修复基因XRCC1单核苷酸多态性及其与食管癌风险的关系[J]．癌症，2001，20(1)：28-31．
63. Lunn RM, Langlois RG, Hsieh LL, et al. XRCC1Polymor-phisms: effects onaflatoxin B12DNA adducts and glycophorin a variant frequency [J]. Cancer Res,1999,59(11):2557-2561.
64. Abdel-Rahman SZ, Soliman AS, Bondly ML, et al. Inheritance of the194Trp andthe399Gln variant alleles of the DNA repair gene XRCC1are associated withincreased risk of early2onset colorectal carcinoma in Egypt [J]. Cancer Let t,2000,159(1):79-86.
65. David-Beabes GL, London SJ. Genetic polymorphism of XRCC1and lung cancerrisk among African2Americans and Caucasians [J]. L ung Cancer,2001,34(3):333-339.
66. Shen MR，Jones IM．Mohrenweiser H．Nonconservative amino acid substitutionvariants exist at polymorphic frequency in DNA repair genes in healthyhumans[J]．Cancer Res，1998，58(4)：604-608．
67.邢德印,齐军,谭文,等.北京地区汉族人群DNA修复基因XPD单核苷酸多态与肺癌及食管癌风险的研究[J].中华医学遗传学杂志,2003,20(1):35-38.
68.梁刚,程家蓉,张学宏,等. DNA修复基因XPD单核苷酸多态与胆道癌遗传易感性[J].肿瘤,2006,26(5):444-449.
69. Butkiewicz D, Rusin M, Enewold L，et al. Genetic polymorphisms in DNA repairgenes and risk of lung cancer. Carcinogenesis.2001r;22(4):593-7.
70.叶家才，崔书中，巴明臣。原发性肝癌的流行病学特征及其危险因素。实用医学杂志2008，24(10)：1839-1841.
71.陈建国,朱健,张永辉,等.江苏省启东地区1973至2002年肝癌发病率长期趋势的评价[J].中华医学杂志,2005,85(43):3052-3056.
72. E1-Serag H B. Epidemiology of hepatocellular carcinoma [J]. Clin LiverDis,2001(5):87-107.
73. Angeline S.Andrew1, Heather H.Nelson, Karl T.Kelsey,. Concordance of multipleanalytical approaches demonstrates a complex relationship between DNA repair geneSNPs, smoking and bladder cancer susceptibility. Carcinogenesis,2006,27(5);1030–1037.
74. Rybarova S, Vecanova J, Hodorova I, et al.Association between polymorphisms ofXRCC1, p53and MDR1genes, the expression of their protein products andprognostic significance in human breast cancer. Med Sci Monit.2011,17(12):354-363.
75. Yu MW, Yang SY, Pan IJ, et al. Polymorphisms in XRCC1and glutathioneS2transferase genes and hepatitis B－related hepatocellular carcinoma [J]. J NatCancer Inst,2003,95(19):1485-1488.
76.孙晓艳，王炳元．饮酒与肝癌[J]．现代医药卫生，2007，23(7)：1007-1008．
77. Yin G, Morita M, Ohnaka K, Toyomura K, et al. Genetic Polymorphisms of XRCC1,Alcohol Consumption, and the Risk of Colorectal Cancer in Japan. J Epidemiol.2012;22(1):64-71。
78. Stern MC, Siegmund KD, Conti DV, Corral R, Haile RW. XRCC1, XRCC3, and XPDpolymorphisms as modifiers of the effect of smoking and alcohol on colorectaladenoma risk. Cancer Epidemiol Biomarkers Prev.2006Dec;15(12):2384-90.
79. Rayjean J，Hung，Janet Hall，et al．Genetic polymorphisms in the base excision repairpathway and cancer risk：A HuGE review[J]．American Journal Epidemiology，2005，162：925-942．
80. Hou SM, F lt S, Angelini S, et al．The XPD variant alleles are associated withincreased aromatic DNA adduct level and lung cancer risk. Carcinogenesis.2002Apr;23(4):599-603.
81.汤伯明,张竹梅,王其军,等.饮酒与肝癌的病例对照研究〔J〕.实用肿瘤学杂志,2002,16(2):88-91.
82. Teufel A，Staib F，Kanzler S，et a1．Genetics of Hepatocellular Carcinoma[J]．WorldJ Gastroenterol，2007，28：13(16)：2271-2282．
83. Manjula Kiran，Roli Saxena， Yogesh K. Chawla，et al．Polymorphism of DNArepair gene XRCC1and hepatitis-related hepatocellular carcinoma risk in Indianpopulation.Mol Cell Biochem (2009)327:7–13.
84. Zeng XY, Qiu XQ, Ji L, et al．Study on the relationship between hepatocellularcarcinoma and the interaction between polymorphisms in DNA repair gene XPD andenvironmental factors. Zhonghua Liu Xing Bing Xue Za Zhi.2009Jul;30(7):702-5.
85. Libin Jia,XinWeiWang,Curtis C. Hepatitis B virus X protein does not influenceessential steps of nucleotide excision repair effected by human liver extracts.Biochem Biophys Res Commun.2003Dec19;312(3):806-10.
86. Turati F, Edefonti V, Talamini R, et al． Family history of liver cancer andhepatocellular carcinoma.2011Nov16. doi:10.1002/hep.24794.
87. Falagan-Lotsch P, Rodrigues MS, Esteves V, et al．XRCC1gene polymorphisms in apopulation sample and in women with a family history of breast cancer from Rio deJaneiro (Brazil). Genet Mol Biol.2009;32(2):255-9.
88. Yousry Mostafa Hussien Amal F. Gharib Hanan A. Awad Rehab A. Karam WaelH. Elsawy. Impact of DNA repair genes polymorphism (XPD and XRCC1)on the riskof breast cancer in Egyptian female patients.
89. L Cheng,M R Spitz,W K Hong,et aI. Reduced expression levels of nucleotideexcision repair genes in lung cancer. Carcinogenesis,2000,21:1527
90. Ulla Voget,Bjorn A,Nexo,et al. ERCCl,XPD and RAl mRNA Ievels inlymphocyles arenot associated with lung cancer risk a prospective study ofDaries.Mutation Res,2006,59(3):88
91. Calandra T, Roger T. Macrophage migration inhibitory factor: a regulator of innateimmunity.Nature Reviews Immunology.2003;3(10):791–800.
92. Simons D, Grieb G, Hristov M, Pallua N, Weber C, Bernhagen J, et al.Hypoxia-induced endothelial secretion of macrophage migration inhibitory factor androle in endothelial progenitor cell recruitment. J Cell Mol Med.2010Epub ahead ofprint.
93. Calandra T, Bernhagen J, Mitchell RA, Bucala R. The macrophage is an importantand previously unrecognized source of macrophage migration inhibitory factor.Journal of Experimental.Medicine.1994;179(6):1895–902.
94. Mitchell RA, Metz CN, Peng T, Bucala R. Sustained mitogen-activated protein kinase(MAPK) and cytoplasmic phospholipase A2activation by macrophage migrationinhibitory factor (MIF).Regulatory role in cell proliferation and glucocorticoid action.Journal of Biological Chemistry.1999;274(25):18100–6.
95. Noh SU, Park YM. The effect of green tea polyphenols on macrophage migrationinhibitory factor-associated steroid resistance.Br J Dermatol.2011Nov4. doi:
10.1111/j.1365-2133.2011.10720.
96. Kofoed K, Andersen O, Kronborg G, Tvede M, Petersen J, Eugen-Olsen J, et al. Useof plasma C-reactive protein, procalcitonin, neutrophils, macrophage migrationinhibitory factor, soluble urokinase-type plasminogen activator receptor, and solubletriggering receptor expressed on myeloid cells-1in combination to diagnoseinfections: a prospective study. Critical Care (London, England).2007;11(2):R38.
97. Bruchfeld A, Carrero JJ, Qureshi AR, Lindholm B, Barany P, Heimburger O, et al.Elevated serum macrophage migration inhibitory factor (MIF) concentrations inchronic kidney disease (CKD) are associated with markers of oxidative stress andendothelial activation. Molecular Medicine.2009;15(3-4):70–5.
98. Chesney J, Metz C, Bacher M, Peng T, Meinhardt A, Bucala R. An essential role formacrophage migration inhibitory factor (MIF) in angiogenesis and the growth of amurine lymphoma.Molecular Medicine.1999;5(3):181–91.
99. Bucala R, Donnelly SC. Macrophage migration inhibitory factor: a probable linkbetween inflammation and cancer. Immunity.2007;26(3):281–5.
100. Hawkins O, Verma B, Lightfoot S, et al. An HLA-presented fragment of macrophagemigration inhibitory factor is a therapeutic target for invasive breast cancer. JImmunol.2011;186(11):6607-16.
101. Shimizu T, Abe R, Nakamura H, Ohkawara A, Suzuki M, Nishihira J. High expressionof macrophage migration inhibitory factor in human melanoma cells and its role intumor cell growth and angiogenesis. Biochemical&Biophysical ResearchCommunications.1999;264(3):751–8.
102. Hudson JD, Shoaibi MA, Maestro R, Carnero A, Hannon GJ, Beach DH. Aproinflammatory cytokine inhibits p53tumor suppressor activity. Journal ofExperimental Medicine.1999;190(10):1375–82.
103. Mor G, Visintin I, Lai Y, Zhao H, Schwartz P, Rutherford T, et al. Serum proteinmarkers for early detection of ovarian cancer. Proceedings of the National Academyof Sciences of the United States of America.2005;102(21):7677–82.
104. Kim K, Visintin I, Alvero AB, Mor G. Development and validation of a protein-basedsignature for the detection of ovarian cancer. Clinics in Laboratory Medicine.2009;29(1):47–55.
105. Shun CT, Lin JT, Huang SP, Lin MT, Wu MS. Expression of macrophage migrationinhibitory factor is associated with enhanced angiogenesis and advanced stage ingastric carcinomas. World Journal of Gastroenterology.2005;11(24):3767–71.
106. Camlica H, Duranyildiz D, Oguz H, Oral EN, Yasasever V. The diagnostic value ofmacrophage migration inhibitory factor (MIF) in gastric cancer. Pathology OncologyResearch.2008;14(1):79–83.
107. Mohri Y, Mohri T, Wei W, Qi YJ, Martin A, Miki C, et al. Identification ofmacrophage migration inhibitory factor and human neutrophil peptides1-3aspotential biomarkers for gastric cancer. British Journal of Cancer.2009;101(2):295–302.
108. Yasasever V, Camlica H, Duranyildiz D, Oguz H, Tas F, Dalay N. Macrophagemigration inhibitory factor in cancer. Cancer Investigation.2007;25(8):715–9.
109. Baugh JA, Chitnis S, Donnelly SC, Monteiro J, Lin X, Plant BJ, et al. A functionalpromoter polymorphism in the macrophage migration inhibitory factor (MIF) geneassociated with disease severity in rheumatoid arthritis. Genes&Immunity.2002;3(3):170–6.
110. Radstake TR, Sweep FC, Welsing P, Franke B, Vermeulen SH, Geurts-Moespot A, etal. Correlation of rheumatoid arthritis severity with the genetic functional variants andcirculating levels of macrophage migration inhibitory factor. Arthritis&Rheumatism.2005;52(10):3020–9.
111. Arisawa T, Tahara T, Shibata T, Nagasaka M, Nakamura M, Kamiya Y, et al.Functional promoter polymorphisms of the macrophage migration inhibitory factorgene in gastric carcinogenesis. Oncology Reports.2008;19(1):223–8.
112. Meyer-Siegler KL, Vera PL, Iczkowski KA, Bifulco C, Lee A, Gregersen PK, et al.Macrophage migration inhibitory factor (MIF) gene polymorphisms are associatedwith increased prostate cancer incidence. Genes&Immunity.2007;8(8):646–52.
113. Morand EF, Leech M, Bernhagen J． MIF a new cytokine link between rheumatoidarthritis and atherosclerosis J.Nature Reviews Drug Discov2005,5399－411．
114.柳爱华，石梅，赵勤等。MIF基因启动子多态性与结核病相关性研究进展。热带医学杂志2010年9月第10卷第9期。
115. Coussens LM, Werb Z. Inflammation and cancer. Nature.2002Dec19-26;420(6917):860-7.
116. Kuper H, Adami HO, Trichopoulos D. Infections as a major preventable cause ofhuman cancer. Journal of Internal Medicine.2000;248(3):171–83.
117. Balkwill F, Mantovani A. Inflammation and cancer: back to Virchow? Lancet.2001;357(9255):539–45.
118. Bucala R, Donnelly SC. Macrophage migration inhibitory factor: a probable linkbetween inflammation and cancer. Immunity.2007;26(3):281–5.
119.邓玮,易永芬,闫田静等，胃癌组织和细胞中P115、M IF的表达及意义。第三军医大学学报。2011；33(3)：241-245。
120.李虎,梁朝朝,郝宗耀等。M IF在前列腺癌组织中的表达及其意义[J].安徽医药,2009；13(11)：1361-1363。
121. Han Y, Zhang C. Macrophage migration inhibitory factor plays a pivotal role inhepatocellular carcinoma and may be a noninvasive imaging target. Med Hypotheses.2010;75(6):530-2.
122. Eiji H，Takashi O，Dipok KD,et a1．Overexpression of macmphage migrationinhibitory factor induces angiogenesis and deteriorates prognosis after radicalresection for hepatocelular carcinoma. Cancer，2005，103：588—596．
123. Donn R，Alourfi Z，De Benedetti F，et a1．Mutation screening of the macrophagemigration inhibitory factor gene：positive association of a functional polymorphism ofmacrophage migration inhibitory factor with juvenile idiopathic arthritis．ArthritisRheum，2002，46：2402-2469．
124. Xia HH, Zhang ST, Lam SK, Lin MC, Kung HF, Wong BC. Expression ofmacrophage migration inhibitory factor in esophageal squamous cell carcinoma andeffects of bile acids and NSAIDs. Carcinogenesis.2005Jan;26(1):11-5.
125. Ren Y, Law S, Huang X, Lee PY, Bacher M, Srivastava G, Wong J. Macrophagemigration inhibitory factor stimulates angiogenic factor expression and correlateswith differentiation and lymph node status in patients with esophageal squamous cellcarcinoma. Ann Surg.2005Jul;242(1):55-63.
126. Omuro, A.M., Delattre, J.Y., What is the place of bevacizumab and irinotecan in thetreatment of glioblastoma and other malignant gliomas? Curr. Opin. Neurol.2008.21,717–719.
127. Sachdev, J.C., Jahanzeb, M., Evolution of bevacizumab-based therapy in themanagement of breast cancer. Clin. Breast Cancer2008.8,402–410.
128. De Benedetti F, Meazza C, Vivarelli M, Rossi F, Pistorio A, Lamb R, et al. Functionaland prognostic relevance of the173polymorphism of the macrophage migrationinhibitory factor gene in systemic-onset juvenile idiopathic arthritis. Arthritis&Rheumatism.2003;48(5):1398–407.
129. Mizue Y, Ghani S, Leng L, McDonald C, Kong P, Baugh J, et al. Role for macrophagemigration inhibitory factor in asthma. Proceedings of the National Academy ofSciences of the United States of America.2005;102(40):14410–5.
130. Wu J, Fu S, Ren X, Jin Y, Huang X, Zhang X, et al. Association of MIF promoterpolymorphisms with childhood asthma in a northeastern Chinese population. TissueAntigens.2009;73(4):302–6.
131. Nohara H, Okayama N, Inoue N, Koike Y, Fujimura K, Suehiro Y, et al. Associationof the173G/C polymorphism of the macrophage migration inhibitory factor genewith ulcerative colitis. Journal of Gastroenterology.2004;39(3):242–6.
132. Donn RP, Plant D, Jury F, Richards HL, Worthington J, Ray DW, et al. Macrophagemigration inhibitory factor gene polymorphism is associated with psoriasis. Journal ofInvestigative Dermatology.2004;123(3):484–7.
133. McDevitt MA, Xie J, Shanmugasundaram G, Griffith J, Liu A, McDonald C, et al. Acritical role for the host mediator macrophage migration inhibitory factor in thepathogenesis of malarial anemia. Journal of Experimental Medicine.2006;203(5):1185–96.
134. Zhong XB, Leng L, Beitin A, Chen R, McDonald C, Hsiao B, et al. Simultaneousdetection of microsatellite repeats and SNPs in the macrophage migration inhibitoryfactor (MIF) gene by thin-film biosensor chips and application to rural field studies.Nucleic Acids Research.2005;33(13):e121.
135. Farinati F, Rinaldi M, Gianni S, et al. How should patients with hepatocellularcarcinoma be staged? Validation of a new prognostic system[J]. Cancer,2000,89(11):2266。
136. Seki T, Tamai T, Nakagawa T, et al. Combination therapy with transcathter arterialchemoembolization and percutaneous microwave coagulation therapy forhepatocellular carcinoma Cancer,2000,89(6):1245。
1. I.Berlin,B.deBrettes,G.Aymard,B.Diquet,L.Arnulf,A.J.Puech.Dopaminergic drugresponse and the genotype(Taq IA polymorphism)of the dopamine D2receptor.Int.J.Neuropsychopharmacol,2000,3;35–43.
2. I. Ieiri, H. Takane, T. Hirota, K. Otsubo, S. Higuchi, Genetic polymorphisms of drugtransporters: pharmacokinetic and pharmacodynamic consequences in pharmacotherapy.Expert Opin. Drug Metab. Toxicol.2006,2;651–674.
3. E. Shikata, I. Ieiri, S. Ishiguro, H. Aono, K. Inoue, T. Koide, S. Ohgi, K.Otsubo,Association of pharmacokinetic (CYP2C9) and pharmacodynamic (factors II,VII,IX, and X; proteins S and C; and g-glutamyl carboxylase) gene variants withwarfarin sensitivity. Blood,2004,103;2630–2635.
4. J.Q. He, J. Ruan, J.E. Connett, N.R. Anthonisen, P.D. Pare′, A.J. Sandford, Antioxidantgene polymorphisms and susceptibility to a rapid decline in lung function in smokers.Am. J. Respir. Crit. Care Med,2002,166;323–328.
5. J.K. Horton, M. Watson, D.F. Stefanick, D.T. Shaughnessy, J.A. Taylor, S.H.Wilson,XRCC1and DNA polymerase β in cellular protection against cytotoxic DNAsingle-strand breaks. Cell Res.2008),18;48–63.
6. O. Mortusewicz, H. Leonhardt, XRCC1and PCNA are loading platforms with distinctkinetic properties and different capacities to respond to multiple DNA lesions. BMC Mol.Biol.2007,8;81.
7. L.H. Thompson, M.G. West, XRCC keeps DNA from getting stranded. Mutat. Res.2000),459;1–18.
8. S. Sterpone, R. Cozzi, Influence of XRCC1genetic polymorphisms on ionizingradiation-induced DNA damage and repair. J. Nucleic Acids,2010.
9. R.S. Tebbs, M.L. Flannery, J.J. Meneses, A. Hartmann, J.D. Tucker, L.H. Thompson,J.E.Cleaver, R.A. Pedersen, Requirement for the XRCC1DNA base excision repair geneduring early mouse development. Dev. Biol.1999,208;513–529.
10. L.H. Thompson, K.W. Brookman, L.E. Dillehay, A.V. Carrano, J.A. Mazrimas,C.L.Mooney, J.L. Minkler, A CHO-cell strain having hypersensitivity to mutagens, adefect in DNA strand-break repair, and an extraordinary baseline frequency of sisterchromatid exchange. Mutat. Res.1982,95(2–3):427–440.
11. L.H. Thompson, K.W. Brookman, N.J. Jones, S.A. Allen, A.V. Carrano, Molecularcloning of the human XRCC1gene, which corrects defective DNA strand break repairand sister chromatid exchange. Mol. Cell. Biol.1990),10(12):6160–6171.
12. R.S. Tebbs, M.L. Flannery, J.J. Meneses, A. Hartmann, J.D. Tucker, L.H. Thompson,J.E.Cleaver, R.A. Pedersen, Requirement for the XRCC1DNA base excision repair geneduring early mouse development. Dev. Biol.1999,208;513–529.
13. R.J. Hung, J. Hall, P. Brennan, P. Boffetta, Genetic polymorphisms in the base excisionrepair pathway and cancer risk: a HuGE review. Am. J. Epidemiol.2005),162(10):925–942.
14. I. Laczmanska, J. Gil, P. Karpinski, A. Stembalska, J. Kozlowska, H. Busza,A.Trusewicz, K. Pesz, D. Ramsey, K. Schlade-Bartusiak, N. Blin, M.M.Sasiadek,Influence of polymorphisms in xenobiotic-metabolizing genes and DNA-repairgenes on diepoxybutane-induced SCE. Environ. Mol. Mutagen.2006,47;666–673.
15. S.Z. Abdel-Rahman, R.A. El-Zein, The399Gln polymorphism in the DNA repair geneXRCC1modulates the genotoxic response induced in human lymphocytes by thetobacco-specific nitrosamine NNK. Cancer Lett.2000,159;63–71.
16. Y. Wang, M.R. Spitz, Y. Zhu, Q. Dong, S. Shete, X. Wu, From genotype to phenotype:correlating XRCC1polymorphisms with mutagen sensitivity. DNA Repair2003,2;901–908.
17. S. Angelini, R. Kumar, F. Carbone, J.L. Bermejo, F. Maffei, G. Cantelli-Forti, K.Hemminki, P. Hrelia, Inherited susceptibility to bleomycin-induced micronuclei:correlatingpolymorphisms in GSTT1, GSTM1and DNA repair genes with mutagen sensitivity.Mutat. Res.2008),638(1–2):90–97.
18. Y. Li, M.J. Marion, J. Zipprich, G. Freyer, R.M. Santella, C. Kanki, P.W.Brandt-Rauf,The role of XRCC1polymorphisms in base excision repair of etheno-DNAadducts in French vinyl chloride workers. Int. J. Occup. Med. Environ. Health,2006,19(1):45–52.
19. P. Vodicka, R. Kumar, R. Stetina, S. Sanyal, P. Soucek, V. Haufroid, M. Dusinska,M.Kuricova, M. Zamecnikova, L. Musak, J. Buchancova, H. Norppa, A. Hirvonen,L.Vodickova, A. Naccarati, Z.Matousu, K.Hemminki, Genetic polymorphisms in DNArepair genes and possible links with DNA repair rates, chromosomal aberrations andsingle strand breaks in DNA. Carcinogenesis,2004),25(5):757–763.
20. W.W. Au, S.A. Salama, C.H. Sierra-Torres, Functional characterization of polymorphisms in DNA repair genes using cytogenetic challenge assays, Environ.Health Perspect.2003,111;1843–1850.
21. S. Marsin, A.E. Vidal, M. Sossou, J. Me′nissier-de Murcia, F. Le Page, S. Boiteux, G.deMurcia, J.P. Radicella, Role of XRCC1in the coordination and stimulation of oxidativeDNA damage repair initiated by the DNA glycosylase hOGG1. J. Biol.Chem.2003,278(45):44068–44074.
22. P. Vodicka, R. Kumar, R. Stetina, S. Sanyal, P. Soucek, V. Haufroid, M. Dusinska,M.Kuricova, M. Zamecnikova, L. Musak, J. Buchancova, H. Norppa, A. Hirvonen,L.Vodickova, A. Naccarati, Z.Matousu, K.Hemminki, Genetic polymorphisms in DNArepair genes and possible links with DNA repair rates, chromosomal aberrations andsingle-strand breaks in DNA. Carcinogenesis,2004,25(5):757–763.
23. A.R. Collins, M. Dusinska′, E. Horva′thova′, E. Munro, M. Savio, R. Ste tina,Interindividual differences in repair of DNA base oxidation. Measured in vitro with thecomet assay. Mutagenesis,2001,16(4):297–301.
24. J. Slyskova, M. Dusinska, M. Kuricova, P. Soucek, L. Vodickova, S. Susova,A.Naccarati, E. Tulupova, P. Vodicka, Relationship between the capacity to repair8-oxoguanine biomarkers of genotoxicity and individual susceptibility in styreneexposedworkers. Mutat. Res.2007,634;101–111.
25. J. Tuimala, G. Szekely, S. Gundy, A. Hirvonen, H. Norppa, Genetic polymorphisms ofDNA repair and xenobiotic-metabolizing enzymes: role in mutagen sensitivity.Carcinogenesis,2002),23(6):1003–1008.
26. B. Hao, X. Miao, Y. Li, X. Zhang, T. Sun, G. Liang, Y. Zhao, Y. Zhou, H. Wang, X.Chen,L. Zhang, W. Tan, Q. Wei, D. Lin, F. He, A novel T-77C polymorphism in DNArepair gene XRCC1contributes to diminished promoter activity and increased risk ofnon-small cell lung cancer. Oncogene,2006,25:3613–3620.
27. L. Liu, P. Yuan, L. Liu, C. Wu, X. Zhang, H. Guo, R. Zhong, Y. Xu, J. Wu, S. Duan,R.Rui, T. Wu, S. Nie, X. Miao, D. Lin, A functional-77T→C polymorphism in XRCC1is associated with risk of breast cancer. Breast Cancer Res. Treat.2010, June13
28. P. Mohamadynejad, M. Saadat, Genetic polymorphisms of XRCC1(at codons194and399) in Shiraz population (Fars Province, Southern Iran). Mol. Biol. Rep.2007,September14。
29. N.A. Kocabas, B. Karahalil, XRCC1Arg399Gln genetic polymorphism in a Turkishpopulation. Int. J. Toxicol.2006,25;419–422.
30. S. Sterpone, V. Mastellone, L. Padua, F. Novelli, C. Patrono, T. Cornetta,D.Giammarino, V. Donato, A. Testa, R. Cozzi, Single-nucleotide polymorphisms in BERand HRR genes. XRCC1haplotypes and breast cancer risk in Caucasian women.J.Cancer Res. Clin. Oncol.2010,136;631–636.
31. R. Brem, D.G. Cox, B. Chapot, N. Moullan, P. Romestaing, J.P. Ge′rard, P. Pisani,J.Hall, The XRCC1-77T> C variant: haplotypes, breast cancer risk, response toradiotherapy and the cellular response to DNA damage. Carcinogenesis,2006,27;2469–2474.
32. R.M. Lunn, R.G. Langlois, L.L. Hsieh, C.L. Thompson, D.A. Bell, XRCC1polymorphisms:effects on aflatoxin B1–DNA adducts and gylcophorin A variantfrequency.Cancer Res,1999,59;2557–2561.
33. E.J. Duell, J.K. Wiencke, T.J. Cheng, A. Varkonyi, Z.F. Zuo, T.D. Ashok, J.E. Mark,J.C.Wain, D.C. Christiani, K.T. Kelsey, Polymorphism in the DNA repair genes XRCC1and ERCC2and biomarkers of DNA damage in human blood mononuclearcells.Carcinogenesis,2000,21;965–971.
34. G. Matullo, D. Palli, M. Peluso, S. Guarrera, S. Carturan, E. Celentano, V. Krogh,A.Munnia, R. Tumino, S. Polidoro, A. Piazza, P. Vineis, XRCC1, XRCC3, XPD genepolymorphisms. Smoking and32P–DNA adducts in a sample of healthysubjects.Carcinogenesis,2001,22(9):1437–1445.
35. G. Ji, A. Gu, P. Zhu, Y. Xia, Y. Zhou, F. Hu, L. Song, S. Wang, X. Wang, Joint effects ofXRCC1polymorphisms and polycyclic aromatic hydrocarbons exposure on sperm DNAdamage and male infertility.Toxicol. Sci.,2010,116;92–98.
36. D. Palli, A. Russo, G. Masala, C. Saieva, S. Guarrera, S. Carturan, A. Munnia,G.Matullo, M. Peluso, DNA adducts levels and DNA repair polymorphisms intraffic-exposed workers and a general population sample.Int,J. Cancer,2001,94;121–127.
37. M. Kuricova, A. Naccarati, R. Kumar, M. Koskinen, S. Sanyal, M. Dusinska, J.Tulinska,L. Vodickova, A. Liskova, E. Jahnova, L. Fuortes, V. Haufroid, K. Hemminki,P. Vodicka,DNA repair and cyclin D1polymorphisms and styreneinduced genotoxicity andimmunotoxicity, Toxicol. Appl. Pharmacol,2005,207; S302–S309.
38. P. Vodicka, R. Kumar, R. Stetina, L. Musak, P. Soucek, V. Haufroid, M. Sasiadek,L.Vodickova, A. Naccarati, J. Sedikova, S. Sanyal, M. Kuricova, V. Brsiak, H. Norppa,J.Buchancova, K. Hemminki, Markers of individual susceptibility and DNA repair rate inworkers exposed to xenobiotics in a tire plant.Environ.Mol. Mutagen,2004,44;283–292.
39. Q. Wang, A.H. Wang, H.S. Tan, N.N. Feng, Y.J. Ye, X.Q. Feng, G. Liu, Y.X. Zheng,Z.L.Xia, Genetic polymorphisms of DNA repair genes and chromosomal damage in workersexposed to1,3-butadiene. Carcinogenesis,2010,31;858–863.
40. Q. Wang, F. Ji, Y. Sun, Y.L. Qiu, W. Wang, F. Wu, W.B. Miao, Y. Li, P.W.Brandt-Rauf,Z.L. Xia, Genetic polymorphisms of XRCC1, HOGG1and MGMT andmicronucleus occurrence in Chinese vinyl chloride-exposed workers. Carcinogenesis,2010,31;1068–1073.
41. N.K. Bolegenova, B.O. Bekmanov, L.B. Djansugurova, R.I. Bersimbaev, S.A.Salama,W.W. Au, Genetic polymorphisms and expression of minisatellite mutations in a3generation population around the Semipalatinsk nuclear explosion test site,Kazakhstan,Int. J. Hyg. Environ. Health,2009,212;654–660.
42. R. Pastorelli, A. Cerri, M. Mezzetti, E. Consonni, L. Airoldi, Effect of DNA repair genepolymorphisms on BPDE–DNA adducts in human lymphocytes. Int. J.Cancer,(2002,100;9–13.
43. J. Shen, M.D. Gammon, M.B. Terry, L. Wang, Q. Wang, F. Zhang, S.L. Teitelbaum,S.M.Eng, S.K. Sagiv, M.M. Gaudet, A.I. Neugut, R.M. Santella, Polymorphisms in XRCC1modify the association between polycyclic aromatic hydrocarbon–DNA adducts,cigarette smoking, dietary antioxidants, and breast cancer risk. Cancer Epidemiol.Biomark. Prev,2005,14(2):336–342.
44. G. Matullo, S. Guarrera, S. Carturan, M. Peluso, C. Malaveille, L. Davico, A. Piazza,P.Vineis, DNA repair gene polymorphisms, bulky DNA adducts in white blood cells andbladder cancer in a case–control study. Int. J. Cancer.2002,92;562–567.
45. Z. Hu, H. Ma, F. Chen, Q. Wei, H. Shen, XRCC1polymorphisms and cancer risk: ameta-analysis of38case–control studies. Cancer Epidemiol. Biomark. Prev.2005,14(7):1810–1818.
46. E.M. Sturgis, E.J. Castillo, L. Li, R. Zheng, A.S. Eicher, G.L. Clayman, S.S. Strom,M.R.Spitz, Q. Wei, Polymorphisms of DNA repair gene XRCC1in squamous cellcarcinoma of the head and neck. Carcinogenesis,1999,20(11):2125–2129.
47. J.M. Lee, Y.C. Lee, S.Y. Yang, P.W. Yan, S.P. Luh, C.J. Lee, C.J. Chen, M.T. Wu,Genetic polymorphisms of XRCC1and risk of the esophageal cancer. Int. J. Cancer,2001,95;240–246.
48. H. Shen, Y. Xu, Y. Qian, R. Yu, Y. Qin, L. Zhou, L. Wang, X. Wang, M.R. Spitz, Q.Wei,Polymorphisms of the DNA repair gene XRCC1and risk of gastric cancer in aChinese population. Int. J. Cancer,2000,88;601–606.
49. S.Z. Abdel-Rahman, A.S. Soliman, M.L. Bondy, S. Omar, S.A. El-Badaway,H.M.Khaled, I.A. Seifeldin, B. Levin, Inheritance of the194Trp and the399Gln variantalleles of the DNA repair gene XRCC1are associated with increased risk of theearly-onset colorectal carcinoma in Egypt. Cancer Lett.2000,159;79–86.
50. C. Wang, Y. Sun, R. Han, XRCC1genetic polymorphisms and bladder cancersusceptibility: a meta-analysis. Urology,2008.
51. T.B. Tumer, D. Yilmaz, C. Tanrikut, G. Sahin, G. Ulusoy, E. Arinc, DNA repair XRCC1Arg399Gln polymorphism alone, and in combination with CYP2E1polymorphismssignificantly contribute to the risk of development of childhood acute lymphoblasticleukemia. Leuk. Res.2010,34;1275–1281.
52. A.H. Gu, J. Lian, N.X. Lu, Y.K. Xia, C.C. Lu, L. Song, S.H. Wang, X.R.Wang,Association of XRCC1gene polymorphisms with idiopathic azoospermia in aChinese population. Asian J. Androl.2007,9(6):781–786.
53. P.L. Chen, K.T. Yeh, Y.Y. Tsai, H. Koeh, Y.L. Liu, H. Lee, Y.W. Cheng, XRCC1, but notAPE1and hOGG1gene polymorphisms is a risk factor for pterygium. Mol. Vis.2010,16;991–996.
54. K. Metsola, V. Kataja, P. Sillanpa¨a¨, P. Siivola, L. Heikinheimo, M. Eskelinen,V.M.Kosma, M. Uusitupa, A. Hirvonen, XRCC1and XPD genetic polymorphisms,smoking and breast cancer risk in a Finnish case–control study. Breast Cancer Res.2005,7(6); R987–R997.
55. B. Thyagarajan, K.E. Anderson, A.R. Folsom, D.R. Jacobs Jr., C.F. Lynch, A. Bargaje,W.Khaliq, M.D. Gross, No association between XRCC1and XRCC3gene polymorphismsand breast cancer risk: Iowa Women’s Health Study. Cancer Detect.Prev.2006,30(4):313–321.
56. A.V. Patel, E.E. Calle, A.L. Pavluck, H.S. Feigelson, M.J. Thun, C. Rodriguez, Aprospective study of XRCC1(X-ray cross-complementing group1) polymorphisms andbreast cancer risk. Breast Cancer Res.2005,7(6): R1168–R1173.
57. S.N. Silva, R. Moita, A.P. Azevedo, R. Gouveia, I. Manita, J.E. Pina, J. Rueff, J.Gaspar,Menopausal age and XRCC1gene polymorphisms: role in breast cancerrisk.Cancer Detect. Prev.2007,31(4):303–309.
58. Y. Zhang, P.A. Newcomb, K.M. Egan, L. Titus-Ernstoff, S. Chanock, R. Welch,L.A.Brinton, J. Lissowska, A. Bardin-Mikolajczak, B. Peplonska, N. Szeszenia-Dabrowska,W. Zatonski, M. Garcia-Closas, Genetic polymorphisms in base-excisionrepair pathway genes and risk of breast cancer. Cancer Epidemiol. Biomark. Prev.2006,15(2):353–358.
59.The Breast Cancer Association Consortium, Commonly studied single-nucleotidepolymorphisms and breast cancer: results from The Breast Cancer AssociationConsortium. J. Natl. Cancer Inst.2006,98(19):1382–1396.
60. H. Li, T.C. Ha, B.C. Tai, XRCC1gene polymorphisms and breast cancer risk indifferent populations: a meta analysis. Breast,2009,18:183–191.
61. D. Butkiewicz, M. Rusin, L. Enewold, P.G. Shields, M. Chorazy, C.C. Harris, Geneticpolymorphisms in DNA repair genes and risk of lung cancer. Carcinogenesis,2001,22;593–597.
62. C. Harms, S.A. Salama, C.H. Sierra-Torres, N. Cajas-Salazar, W.W. Au, Polymorphismsin DNA repair genes, chromosome aberrations and lung cancer. Environ.Mol. Mutagen.2004,44;74–82.
63. D. Ratnasinghe, S.X. Yao, J.A. Tangrea, Y.L. Qiao, M.R. Anderson, M.J. Barrett,C.A.Giffen, Y. Erozan, M.S. Tockman, P.R. Taylor, Polymorphisms of the DNA repairgene XRCC1and lung cancer risk. Cancer Epidemiol. Biomark. Prev.2001,10(2);119–123.
64. G.L. David-Beabes, S.J. London, Genetic polymorphisms of XRCC1and lung cancerrisk among African-Americans and Caucasians. Lung Cancer,2001,34333–339.
65. R.J. Hung, P. Brennan, F. Canzian, N. Szeszenia-Dabrowska, D. Zaride, J. Lissowska,P.Rudnai, E. Fabianova, D. Mates, L. Foretova, V. Janout, V. Bencko, A. Chabrier, S.Borel,J. Hall, P. Boffetta, Large-scale investigation of base excision repair geneticpolymorphisms and lung cancer risk in a multicenter study. J. Natl. Cancer Inst.2005,97;56–76.
66. K.K. Divine, F.D. Gilliland, R.E. Crowell, C.A. Stidley, T.J. Bocklage, D.L. Cook,S.A.Belinsky, The XRCC1399glutamine allele is a risk factor for adenocarcinoma ofthe lung, Mutat. Res.2001,273–278.
67. J.Y. Park, S.Y. Lee, H.S. Jeon, N.C. Bae, S.C. Chae, S. Joo, C.H. Kim, J.H. Park, S.Kam,S.I. Kim, T.H. Jung, Polymorphism of the DNA repair gene XRCC1and risk ofprimary lung cancer. Cancer Epidemiol. Biomark. Prev.2002,11;23–27.
68. C. Kiyohara, K. Takayama, Y. Nakanishi, Association of genetic polymorphisms in thebase excision repair pathway with lung cancer risk: a meta-analysis. Lung Cancer,2006,54(3):267–283.
69. J. Schneider, V. Classen, S. Helmig, XRCC1polymorphism and lung cancer risk.ExpertRev. Mol. Diagn.2008,8;761–780.
70. J.D. Figueroa, N. Malats, F.X. Real, D. Silverman, M. Kogevinas, S. Chanock, R.Welch,M. Dosemeci, A. Tardon, C. Serra, A. Carrato, R. Garcia-Closas, G.C. Vinyals,N.Rothman, M. Garcia Clonas, Genetic variation in the base excision repair pathway andbladder cancer risk. Hum. Genet.2007,121;233–242.
71. S.C. Sak, J.H. Barrett, A.B. Paul, D.T. Bishop, A.E. Kiltie, DNA repair gene XRCC1polymorphisms and bladder cancer risk. BMC Genet.2007,8;13.
72. M.J. Felini, A.F. Oslhan, J.C. Schroeder, K.E. North, S.E. Carozza, K.T. Kelsey, M.Liu,T. Rice, J.K. Wiencke, M.R. Wrensch, DNA repair polymorphisms XRCC1andMGMT and risk of adult gliomas. Neuroepidemiology,2007,29;55–58.
73. J. Geng, Y.W. Zhang, G.C. Huang, L.B. Chen, XRCC1genetic polymorphismArg399Gln and gastric cancer risk: a meta-analysis. World J. Gastroenterol.2008,14;6733–6737.
74. D. Xing, J. Qi, X. Miao, W. Lu, W. Tan, D. Lin, Polymorphisms of DNA repair genesXRCC1and XPD and their associations with risk of esophageal squamous cellcarcinoma in a Chinese population. Int. J. Cancer2002,100;600–605.
75. R.C. Sobti, J. Singh, P. Kaur, S.S. Pachouri, E.A. Siddiqui, H.S. Bindra, XRCC1codon399and ERCC1codon751polymorphism, smoking, and drinking and risk of esophagealsquamous cell carcinoma in a North Indian population. CancerGenet. Cytogenet.2007,175;91–97.
1. Weber C A,Salazar E P,Stewart S A,et aI. ERCC2:cDNA cloning and molecularcharacterization of a human nucleotide excision repair gene with hgh homology to yeastRAD3. EMBO J,1990,9(5):1437。
2.蒋易,周李承,吴晓明,周宜开,雷于生,任恕.核苷酸切除修复基因XPD反义RNA表达载体的构建及功能研究[J].华中科技大学学报(医学版),2003,(03)。
3. Richard D W. Nucleotide excision repair in mammalian cells. J Biol Chem.1997Sep19;272(38):23465-8。
4. Lunn RM, Helzlsouer KJ, Parshad R, Umbach DM, Harris EL, Sanford KK, Bell DA.XPD polymorphisms: effects on DNA repair proficiency。 Carcinogenesis.2000Apr;21(4):551-5.
5. Shen MR, Jones IM, Mohrenweiser H. Nonconservative amino acid substitutionvariants exist at polymorphic frequency in DNA repair genes in healthy humans。CancerRes.1998Feb15;58(4):604-8.
6. Yang L,Parkin D M,Li L,et al. Time trends in cancer mortality in China:1987-1999.Int J Cancer,2003,106(5):771。
7. Misra R R, Ratnasinghe D, Tangrea J A, et al. Polymorphisms in the DNA repairgenes XPD,XRCCl,XRCC3,and APEIref-1. and the risk of lung cancer among malesmokers in Finland. Cancer Lett,2003,191(5):171。
8. Hou SM,Falt S,Angelini S,et al. The XPD variant alleles are associated with increasedaromatic DNA adduct level and lung cancer risk. Carcinogenesis,2002,23(5):599
9. Popanda O, Schattanberg T, Zaplana J, et al. Specific combinations of DNA repairgene variants and increased for non－small cell lung cancer.Carcinogen,2004,25(12):2433
10. Liang G,Xing D,Miao X,et al. Sequence variations in the DNA repair gene XPD andrisk of lung cancer in a Chincse population,Int J Cancer,2003,105(5):669
11. M Felicitas Lopez-Cima,Patricia GonzaleZ-Arriaga,Laura Garcia-Castro,et al.Polymorphisims in XPC,XPD,XRCC1,and XRCC3DNA repair genes and lungCancer risk in a population of Northem Spain.BMC Cancer,2007,10(7):162
12. Sturgis EM，Zheng R，Li I，et a1．XPD/ERCC2polymorphisms and risk of head andneck cancer：a ease．eontrol analysis．Carcinogenesis，2000，2l：2219—2223．
13. Goode EL，Ulrich CM，Potter JD，et a1．Polymorphisins in DNA repair genes andassociations with cancer risk．Cancer Epi—denfiol Biomarkers Prey，2002．11：1513一l530．
14. Dybdahl M，Frentz G，Vogel U，et a1．Low DNA repair is a risk factor in skincarcinogenesis：a study of basal cell carcinomain psoriasis patients．Mutat Res，1999，433：15-22。
15. Vogel U，Olsen A，Wallin H，et a1．Effectof polymorphisms in XPD，RAI，ASE-1and ERCC1on the risk of basal cell earci-noma among Caucasians after age50.CancerDetect Prev，2005，29：209-214．
16. Tomescu D．Kavanagh G。Ha T．et a1．Nu-cleotide excision repair gene XPDpoly-inorphisms and genetic predisposition to melanoma．Carcinogenesis，2001，22：403-408．
17. Baccarelli A，Calista D，Minghetti P，et a1．XPD gene polymorphism and hostcharac-teristics in the association with cutaneous malignant melanoma risk．Br JCancer，2004，90：497．502．
18. Yuan L, Cui D, Zhao EJ, Jia CZ, Wang LD, Lu WQ.XPD Lys751Gln polymorphism andesophageal cancer risk: a meta-analysis involving2288cases and4096controls. WorldJ Gastroenterol.2011May14;17(18):2343-8.
19. Yu HP，Wang XL，Sun X，el a1．Polymorphisms in the DNA repair gene XPI) andsusceptibility to esophageal squamous cell carcinoma．Cancer Genet Cytogenet，2004，154：10—15．
20. Ye W，Kumar R，Bacova G，et a1．The XPD751GIn allele is associated with anincreased risk for esophageal adenocarci—noma： a population—based case—controlstudy in Sweden．Carcinogenesis，2006，27：1835-1841．
21. Wang F，Chang D，Hu FL，et a1．DNA repair gene XPD polymorphisms and cancerrisk：a meta-analysis based on56case—control studies．Cancer Epidemiol BiomarkersPrey，2008，17：507-517．
22.张传臻,陈自平,徐昌青,宁涛,李丹萍,厚瑞萍. XPD基因与胃癌易感性的相关性[J].癌症,2009,(11)
23.娄毅，宋清斌，何向民，等．东北地区汉族人群DNA修复基因XPD单核苷酸多态性与胃癌的相关性．世界华人消化杂志，2006，14：3143-3146．
24. Huang WY， Chow WH， Rothman N， et al． Selected DNA repair polymorphismsand gastric cancer in Poland ［J］．Carcinogenesis，2005，26(8)：1354－1359．
25. Ye W， Kumar R， Bacova G， et al． The XPD751Gln allele is associated with anincreased risk for esophageal adenocarcinoma： a population-based case-control studyin Sweden ［J］． Carcinogenesis，2006，27(9)：1835－1841．
26. Ruzzo A，Canestrari E， Maltese P， et al． Polymorphisms in genes involved in DNArepair and metabolism of xenobiotics in individual susceptibility to sporadic diffusegastric cancer［J］． Clin Chem Lab Med，2007，45(7)：822－828．
27. McWilliams RR，Bamlet WR，Cunningham JM，et a1．Polymorphisms in DNA repairgenes，smoking，and pancreatic adenoearcinonm risk．Cancer Res，2008，68：4928－4935．
28. Li J， Manal MH， Melissa LB， et a1．The XPD Asp312Asn and Lys751GinPolymor—phisms，corresponding haplotype and pancreatic cancer risk．Cancer Lett，2007，245：61458．
29. Chen CC, Yang SY, Liu CJ等。Association of cytokine and DNA repair genepolymorphisms with hepatitis B-related hepatocellular carcinoma. Int J Epidemiol.2005Dec;34(6):1310-8. Epub2005Sep19.
30.曾小云，仇小强，纪龙，等．DNA修复基因XPD单核苷酸多态性和环境因素的交互作用与肝细胞癌的关联研究．中华流行病学杂志，2009，30：702-705．
31.许丽，吴一迁，金晏，等．DNA修复基因XPD多态性和肝细胞肝癌危险性的病例一对照研究．肿瘤，2004，24：526-529。
32. Long XD, Ma Y, Zhou YF, Yao JG, Ban FZ, Huang YZ, Huang BC. XPD codon312and751polymorphisms, and AFB1exposure, and hepatocellular carcinoma risk. BMCCancer.2009Nov17;9:400.
33. Zhang Y, Ding D, Wang X, Zhu Z, Huang M, He X. Lack of association between XPDLys751Gln and Asp312Asn polymorphisms and colorectal cancer risk: a meta-analysisof case-control studies. Int J Colorectal Dis.2011Oct;26(10):1257-64.
34. Stern MC, Johnson LR, Bell DA, Taylor JA. XPD codon751polymorphism,metabolism genes, smoking, and bladder cancer risk. Cancer Epidemiol BiomarkersPrev.2002Oct;11(10Pt1):1004-11.
35. Li C, Jiang Z, Liu X. XPD Lys(751)Gln and Asp (312)Asn polymorphisms and bladdercancer risk: a meta-analysis.
1. Rich AR, Lewis MR. The nature of allergy in tuberculosis as revealed by tissue culturestudies.Bull Johns Hopkins Hosp.1932;50:115–31.
2. George M, Vaughn JH. In vitro cell migration as a model for delayed hypersensitivity.Proc Soc Exp Biol Mes.1962;111:514–21.
3. David JR. Delayed hypersensitivity in vitro: its mediation by cell-free substancesformed by lymphoid cell-antigen interaction. Proceedings of the National Academy ofSciences of the United States of America.1966;56(1):72–7.
4. Bernhagen J, Calandra T, Mitchell RA, Martin SB, Tracey KJ, Voelter W, et al. MIF is apituitary derived cytokine that potentiates lethal endotoxaemia. Nature.1993;365(6448):756–9.
5. Bernhagen J, Krohn R, Lue H, Gregory JL, Zernecke A, Koenen RR, et al. MIF is anoncognate ligand of CXC chemokine receptors in inflammatory and atherogenic cellrecruitment. Nat Med.May;200713(5):587–96.
6. Calandra T, Roger T. Macrophage migration inhibitory factor: a regulator of innateimmunity.Nature Reviews Immunology.2003;3(10):791–800.
7. Simons D, Grieb G, Hristov M, Pallua N, Weber C, Bernhagen J, et al. Hypoxia-inducedendothelial secretion of macrophage migration inhibitory factor and role in endothelialprogenitor cell recruitment. J Cell Mol Med.2010Epub ahead of print.
8. Calandra T, Bernhagen J, Mitchell RA, Bucala R. The macrophage is an important andpreviously unrecognized source of macrophage migration inhibitory factor. Journal ofExperimental.Medicine.1994;179(6):1895–902.
9. Mitchell RA, Metz CN, Peng T, Bucala R. Sustained mitogen-activated protein kinase(MAPK) and cytoplasmic phospholipase A2activation by macrophage migrationinhibitory factor (MIF).Regulatory role in cell proliferation and glucocorticoid action.Journal of Biological Chemistry.1999;274(25):18100–6.
10. Mitchell RA, Liao H, Chesney J, Fingerle-Rowson G, Baugh J, David J, et al.Macrophage migration inhibitory factor (MIF) sustains macrophage proinflammatoryfunction by inhibiting p53: regulatory role in the innate immune response. Proceedingsof the National Academy of Sciences of the United States of America.2002;99(1):345–50.
11. Leng L, Metz CN, Fang Y, Xu J, Donnelly S, Baugh J, et al. MIF signal transductioninitiated by binding to CD74. Journal of Experimental Medicine.2003;197(11):1467–76.
12. Shi X, Leng L, Wang T, Wang W, Du X, Li J, et al. CD44is the signaling component ofthe macrophage migration inhibitory factor-CD74receptor complex. Immunity.2006;25(4):595–606.
13. Petrovsky N, Socha L, Silva D, Grossman AB, Metz C, Bucala R. Macrophagemigration inhibitory factor exhibits a pronounced circadian rhythm relevant to its roleas a glucocorticoid counter-regulator. Immunology&Cell Biology.2003;81(2):137–43.
14. Bacher M, Metz CN, Calandra T, Mayer K, Chesney J, Lohoff M, et al. An essentialregulatory role for macrophage migration inhibitory factor in T-cell activation.Proceedings of the National Academy of Sciences of the United States of America.1996;93(15):7849–54.
15. Rossi AG, Haslett C, Hirani N, Greening AP, Rahman I, Metz CN, et al. Humancirculating eosinophils secrete macrophage migration inhibitory factor (MIF). Potentialrole in asthma. Journal of Clinical Investigation.1998;101(12):2869–74.
16. Calandra T, Echtenacher B, Roy DL, Pugin J, Metz CN, Hultner L, et al. Protectionfrom septic shock by neutralization of macrophage migration inhibitory factor. NatureMedicine.2000;6(2):164–70.
17. Lehmann LE, Novender U, Schroeder S, Pietsch T, von Spiegel T, Putensen C, et al.Plasma levels of macrophage migration inhibitory factor are elevated in patients withsevere sepsis.Intensive Care Medicine.2001;27(8):1412–5.
18. de Mendonca-Filho HT, Gomes RV, de Almeida Campos LA, Tura B, Nunes EM,Gomes R, et al. Circulating levels of macrophage migration inhibitory factor areassociated with mild pulmonary dysfunction after cardiopulmonary bypass. Shock.2004;22(6):533–7.
19. Kofoed K, Andersen O, Kronborg G, Tvede M, Petersen J, Eugen-Olsen J, et al. Use ofplasma C-reactive protein, procalcitonin, neutrophils, macrophage migration inhibitoryfactor, soluble urokinase-type plasminogen activator receptor, and soluble triggeringreceptor expressed on myeloid cells-1in combination to diagnose infections: aprospective study. Critical Care (London, England).2007;11(2):R38.
20. Sprong T, Pickkers P, Geurts-Moespot A, van der Ven-Jongekrijg J, Neeleman C, KnaupM, et al. Macrophage migration inhibitory factor (MIF) in meningococcal septic shockand experimental human endotoxemia. Shock.2007;27(5):482–7.
21. Emonts M, Sweep FC, Grebenchtchikov N, Geurts-Moespot A, Knaup M, Chanson AL,et al.Association between high levels of blood macrophage migration inhibitory factor,inappropriate adrenal response, and early death in patients with severe sepsis. ClinicalInfectious Diseases.2007;44(10):1321–8.
22. Ostergaard C, Benfield T. Macrophage migration inhibitory factor in cerebrospinal fluidfrom patients with central nervous system infection. Critical Care (London, England).2009;13(3):R101.
23. Rahman SH, Menon KV, Holmfield JH, McMahon MJ, Guillou JP. Serum macrophagemigration inhibitory factor is an early marker of pancreatic necrosis in acutepancreatitis. Annals of Surgery.2007;245(2):282–9.
24. Otukesh H, Fereshtehnejad SM, Hoseini R, Hekmat S, Chalian H, Chalian M, et al.Urine macrophage migration inhibitory factor (MIF) in children with urinary tractinfection: a possible predictor of acute pyelonephritis. Pediatric Nephrology.2009;24(1):105–11.
25. Leech M, Metz C, Hall P, Hutchinson P, Gianis K, Smith M, et al. Macrophagemigration inhibitory factor in rheumatoid arthritis: evidence of proinflammatoryfunction and regulation by glucocorticoids. Arthritis&Rheumatism.1999;42(8):1601–8.
26. Kim HR, Park MK, Cho ML, Yoon CH, Lee SH, Park SH, et al. Macrophage migrationinhibitory factor upregulates angiogenic factors and correlates with clinical measures inrheumatoid arthritis. Journal of Rheumatology.2007;34(5):927–36.
27. Lan HY, Bacher M, Yang N, Mu W, Nikolic-Paterson DJ, Metz C, et al. The pathogenicrole of macrophage migration inhibitory factor in immunologically induced kidneydisease in the rat.Journal of Experimental Medicine.1997;185(8):1455–65.
28. Taniguchi Y, Yorioka N, Yamashita K, Masaki T, Yamakido M. Macrophage migrationinhibitory factor in IgA nephropathy. Kidney International.1998;54(6):2245–6.
29. Taniguchi Y, Yorioka N, Yamashita K, Masaki T, Yamakido M. Expression ofmacrophage migration inhibitory factor in patients with myeloperoxidaseanti-neutrophil cytoplasmic antibody-associated glomerulonephritis. ClinicalNephrology.2000;54(2):147–50.
30. Bruchfeld A, Carrero JJ, Qureshi AR, Lindholm B, Barany P, Heimburger O, et al.Elevated serum macrophage migration inhibitory factor (MIF) concentrations inchronic kidney disease (CKD) are associated with markers of oxidative stress andendothelial activation. Molecular Medicine.2009;15(3-4):70–5.
31. Foote A, Briganti EM, Kipen Y, Santos L, Leech M, Morand EF. Macrophage migrationinhibitory factor in systemic lupus erythematosus. Journal of Rheumatology.2004;31(2):268–73.
32. Wu SP, Leng L, Feng Z, Liu N, Zhao H, McDonald C, et al. Macrophage migrationinhibitory factor promoter polymorphisms and the clinical expression of scleroderma.Arthritis&Rheumatism.2006;54(11):3661–9.
33. Ohwatari R, Fukuda S, Iwabuchi K, Inuyama Y, Onoe K, Nishihira J. Serum level ofmacrophage migration inhibitory factor as a useful parameter of clinical course inpatients with Wegener’s granulomatosis and relapsing polychondritis. Annals ofOtology, Rhinology&Laryngology.2001;110(11):1035–40.
34. Calandra T, Bernhagen J, Metz CN, Spiegel LA, Bacher M, Donnelly T, et al. MIF as aglucocorticoid-induced modulator of cytokine production. Nature.1995;377(6544):68–71.
35. Fingerle-Rowson G, Koch P, Bikoff R, Lin X, Metz CN, Dhabhar FS, et al. Regulationof macrophage migration inhibitory factor expression by glucocorticoids in vivo.American Journal of Pathology.2003;162(1):47–56.
36. Flaster H, Bernhagen J, Calandra T, Bucala R. The macrophage migration inhibitoryfactorglucocorticoid dyad: regulation of inflammation and immunity. MolecularEndocrinology.2007;21(6):1267–80.
37. Otukesh H, Chalian M, Hoseini R, Chalian H, Hooman N, Bedayat A, et al. Urinemacrophage migration inhibitory factor in pediatric systemic lupus erythematosus.Clinical Rheumatology.2007;26(12):2105–7.
38. Yamaguchi E, Nishihira J, Shimizu T, Takahashi T, Kitashiro N, Hizawa N, et al.Macrophage migration inhibitory factor (MIF) in bronchial asthma. Clinical&Experimental Allergy.2000;30(9):1244–9.
39. Bargagli E, Olivieri C, Nikiforakis N, Cintorino M, Magi B, Perari MG, et al. Analysisof macrophage migration inhibitory factor (MIF) in patients with idiopathic pulmonaryfibrosis.Respiratory Physiology&Neurobiology.2009;167(3):261–7.
40. Kuper H, Adami HO, Trichopoulos D. Infections as a major preventable cause ofhuman cancer.Journal of Internal Medicine.2000;248(3):171–83.
41. Coussens LM, Werb Z. Inflammation and cancer. Nature.2002;420(6917):860–7.
42. Balkwill F, Mantovani A. Inflammation and cancer: back to Virchow? Lancet.2001;357(9255):539–45.
43. Bucala R, Donnelly SC. Macrophage migration inhibitory factor: a probable linkbetween inflammation and cancer. Immunity.2007;26(3):281–5.
44. Chesney J, Metz C, Bacher M, Peng T, Meinhardt A, Bucala R. An essential role formacrophage migration inhibitory factor (MIF) in angiogenesis and the growth of amurine lymphoma.Molecular Medicine.1999;5(3):181–91.
45. Shimizu T, Abe R, Nakamura H, Ohkawara A, Suzuki M, Nishihira J. High expressionof macrophage migration inhibitory factor in human melanoma cells and its role intumor cell growth and angiogenesis. Biochemical&Biophysical ResearchCommunications.1999;264(3):751–8.
46. Hudson JD, Shoaibi MA, Maestro R, Carnero A, Hannon GJ, Beach DH. Aproinflammatory cytokine inhibits p53tumor suppressor activity. Journal ofExperimental Medicine.1999;190(10):1375–82.
47. Repp AC, Mayhew ES, Apte S, Niederkorn JY: Human uveal melanoma cells producemacrophage migration-inhibitory factor to prevent lysis by NK cells. J Immunol2000;165:710–715.
48. Abe R, Peng T, Sailors J, Bucala R, Metz CN:Regulation of the CTL response bymacrophage migration inhibitory factor. J Immunol2001;166:747–753.
49. Meyer-Siegler KL, Bellino MA, Tannenbaum M: Macrophage migration inhibitoryfactor evaluation compared with prostate specific antigen as a biomarker in patientswith prostate carcinoma. Cancer2002;94:1449–1456.
50. Hira E, Ono T, Dhar DK, El-Assal ON, Hishikawa Y, Yamanoi A, Nagasue N:Overexpression of macrophage migration inhibitory factor induces angiogenesis anddeteriorates prognosis after radical resection for hepatocellular carcinoma. Cancer2005;103:588–598.
51. Legendre H, Decaestecker C, Nagy N, Hendlisz A, Schuring MP, Salmon I, GabiusHJ,Pector JC, Kiss R: Prognostic values of galectin-3and the macrophage migrationinhibitory factor (MIF) in human colorectal cancers.Mod Pathol2003;16:491–504.
52. Rogge L: A genomic view of helper T cell subsets.Ann NY Acad Sci2002;975:57–67.
53. Mitchell RA, Liao H, Chesney J, Fingerle-Rowson G, Baugh J, David J, Bucala R:Macrophage migration inhibitory factor (MIF) sustains macrophage proinflammatoryfunction by inhibiting p53: regulatory role in the innate immune response. Proc NatlAcad Sci USA2002;99:345–350.
54. Mitchell RA: Mechanisms and effectors of MIF-dependent promotion oftumourigenesis.Cell Signal2004;16:13–19.
55. Onodera S, Suzuki K, Matsuno T, Kaneda K,Takagi M, Nishihira J: Macrophagemigration inhibitory factor induces phagocytosis of foreign particles by macrophages inautocrine and paracrine fashion. Immunology1997;92:131–137.
56. Takahashi N, Nishihira J, Sato Y, Kondo M,Ogawa H, Ohshima T, Une Y, Todo S:Involvement of macrophage migration inhibitory factor (MIF) in the mechanism oftumor cell growth. Mol Med1998;4:707–714.
57. Meyer-Siegler KL, Iczkowski KA, Leng L,Bucala R, Vera PL: Inhibition ofmacrophage migration inhibitory factor or its receptor (CD74) attenuates growth andinvasion of DU-145prostate cancer cells. J Immunol2006;177:8730–8739.
58. Rendon BE, Roger T, Teneng I, Zhao M, Al-Abed Y, Calandra T, Mitchell RA:Regulation of human lung adenocarcinoma cell migration and invasion by macrophagemigration inhibitory factor. J Biol Chem2007;282:29910–29918.
59. Amin MA, Volpert OV, Woods JM, Kumar P,Harlow LA, Koch AE: Migrationinhibitory factor mediates angiogenesis via mitogenactivated protein kinase andphosphatidylinositol kinase. Circ Res2003;93:321–329.
60. Bacher M, Schrader J, Thompson N, Kuschela K, Gemsa D, Waeber G, Schlegel J:Up-regulation of macrophage migration inhibitory factor gene and protein expressionin glial tumor cells during hypoxic and hypoglycemic stress indicates a critical role forangiogenesis in glioblastoma multiforme. Am J Pathol2003;162:11–17.
61. Baugh JA, Gantier M, Li L, Byrne A, Buckley A, Donnelly SC: Dual regulation ofmacrophage migration inhibitory factor (MIF) expression in hypoxia by CREB andHIF-1. Biochem Biophys Res Commun2006;347:895–903.
62. Welford SM, Bedogni B, Gradin K, Poellinger L, Broome Powell M, Giaccia AJ:HIF1-α delays premature senescence throughthe activation of MIF. Genes Dev2006;20:3366–3371.
63. Winner M, Koong AC, Rendon BE, Zundel W, Mitchell RA: Amplification of tumorhypoxic responses by macrophage migration inhibitory factor-dependenthypoxia-inducible factor stabilization. Cancer Res2007;67:186–193.
64. Fingerle-Rowson G, Petrenko O, Metz CN,Forsthuber TG, Mitchell R, Huss R, MollU,Muller W, Bucala R: The p53-dependent effects of macrophage migration inhibitoryfactor revealed by gene targeting. Proc Natl Acad Sci USA2003;100:9354–9359.
65. Petrenko O, Fingerle-Rowson G, Peng T,Mitchell RA, Metz CN: Macrophage migrationinhibitory factor deficiency is associated with altered cell growth and reducedsusceptibility to ras-mediated transformation. J Biol Chem2003;278:11078–11085.
66. Nemajerova A, Mena P, Fingerle-Rowson G,Moll UM, Petrenko O: Impaired DNAdamage checkpoint response in MIF-deficient mice. EMBO J2007.
67. Winner M, Leng L, Zundel W, Mitchell RA:Macrophage migration inhibitory factormanipulation and evaluation in tumoral hypoxic adaptation. Methods Enzymol2007;435:355–369.
68. Altinoz MA, Korkmaz R: NF-κB, macrophage migration inhibitory factor andcyclooxygenase-inhibitions as likely mechanisms behind the acetaminophen-andNSAID-prevention of the ovarian cancer. Neoplasma2004;51:239–247.
69. Mor G, Visintin I, Lai Y, Zhao H, Schwartz P, Rutherford T, et al. Serum proteinmarkers for early detection of ovarian cancer. Proceedings of the National Academy ofSciences of the United States of America.2005;102(21):7677–82.
70. Kim K, Visintin I, Alvero AB, Mor G. Development and validation of a protein-basedsignature for the detection of ovarian cancer. Clinics in Laboratory Medicine.2009;29(1):47–55.
71. Ren Y, Law S, Huang X, Lee PY, Bacher M, Srivastava G, et al. Macrophage migrationinhibitory factor stimulates angiogenic factor expression and correlates withdifferentiation and lymph node status in patients with esophageal squamous cellcarcinoma. Annals of Surgery.2005;242(1):55–63.
72. Shun CT, Lin JT, Huang SP, Lin MT, Wu MS. Expression of macrophage migrationinhibitory factor is associated with enhanced angiogenesis and advanced stage ingastric carcinomas. World Journal of Gastroenterology.2005;11(24):3767–71.
73. Camlica H, Duranyildiz D, Oguz H, Oral EN, Yasasever V. The diagnostic value ofmacrophage migration inhibitory factor (MIF) in gastric cancer. Pathology OncologyResearch.2008;14(1):79–83.
74. Mohri Y, Mohri T, Wei W, Qi YJ, Martin A, Miki C, et al. Identification of macrophagemigration inhibitory factor and human neutrophil peptides1-3as potential biomarkersfor gastric cancer. British Journal of Cancer.2009;101(2):295–302.
75. Yasasever V, Camlica H, Duranyildiz D, Oguz H, Tas F, Dalay N. Macrophagemigration inhibitory factor in cancer. Cancer Investigation.2007;25(8):715–9.
76. Baugh JA, Chitnis S, Donnelly SC, Monteiro J, Lin X, Plant BJ, et al. A functionalpromoter polymorphism in the macrophage migration inhibitory factor (MIF) geneassociated with disease severity in rheumatoid arthritis. Genes&Immunity.2002;3(3):170–6.
77. Radstake TR, Sweep FC, Welsing P, Franke B, Vermeulen SH, Geurts-Moespot A, et al.Correlation of rheumatoid arthritis severity with the genetic functional variants andcirculating levels of macrophage migration inhibitory factor. Arthritis&Rheumatism.2005;52(10):3020–9.
78. Meyer-Siegler KL, Vera PL, Iczkowski KA, Bifulco C, Lee A, Gregersen PK, et al.Macrophage migration inhibitory factor (MIF) gene polymorphisms are associated withincreased prostate cancer incidence. Genes&Immunity.2007;8(8):646–52.
79. Arisawa T, Tahara T, Shibata T, Nagasaka M, Nakamura M, Kamiya Y, et al. Functionalpromoter polymorphisms of the macrophage migration inhibitory factor gene in gastriccarcinogenesis. Oncology Reports.2008;19(1):223–8.
2. Jemal A, Bray F, Center MM, Ferlay J, et a1．Global cancer statistics. CA Cancer JClin.2011Mar-Apr;61(2):69-90.
3. Thomas MB and Zhu AX．Hepatocellular Carcinoma：The Need for progress[J]．JClin Oncol，2005，23(13)：2892-2899.
4. Kuang SY，Jackson PE，Wang JB，et al．Specific mutations of hepatitis B virus inplasma predict liver cancer development[J]．Proc Natl Acad Sci USA，2004，101(10)：3575-3580。
5. Parkin DM， Bray F， Ferlay J， et a1．Global cancer statistics，2002[J]． CACancer J Clin，2005，55(2)：74-108.
6.杨广顺，吴志全，吴孟超．原发性肝癌的规范化综合治疗[J]．中华外科杂志，2001，39(10)：742-744．
7.郑莹,李德錄,沈玉珍,向詠梅,鲍萍萍.上海市原发性肝癌流行状况和趋势分析[J].外科理论与实践，2004,(04)：292-294.
8.曾运红,谭卫仙.原发性肝癌发病主要危险因素的Meta分析〔J〕.现代预防医学,2004,31(2):172–174。
9. Ljumovic D, Diamantis I, A1egakis AK. Differential expression of matrixmetalloproteinase in viral and non2viral chronic liver diseases〔J〕. Chin Chim Acta,2004,349:203–211.
10. Catela Ivkowia T, Loncar B, Spaventi R,et al.Association of H-ras polymorphismsand susceptibility to sporadic colon cancer [J]. Int J Oncol,2009，35(5)：1169-1173.
11. Zhang Y, Jin M, Liu B, et al. Association between H-RAS T81C geneticpolymorphism and gast rointestinal cancer risk: a population based case-controlstudy in China [J]. BMC Cancer,2008,8(5):256.
12.谢锋，徐峰，黄杨卿，等．单核苷酸多态性与肝细胞癌遗传易感性．肝脏，2006，11(6)：413-415．
13. Wang DG，Fan JB，Siao CJ，et al．Large-scale identification，mapping andgenotyping of single-nucleotide polymorphisms in the human genome[J]．Science，1998，280(5366)：1077-1082。
14. Sehl M E, Langer L R, Papp J C, et al. Associations between single nucleotidepolymorphisms in double2st randed DNA repair pat hway genes and familial breastcancer [J]. Clin Cancer Res,2009,15(6):2192-2203.
15. Walsh T, King M C. Ten genes for inherited breast cancer [J].Cancer Cell,2007,11(2):103-105.
16. I. Ieiri, H. Takane, T. Hirota, K. Otsubo, S. Higuchi, Genetic polymorphisms of drugtransporters: pharmacokinetic and pharmacodynamic consequences inpharmacotherapy. Expert Opin. Drug Metab. Toxicol.2006,2;651–674.
17. E. Shikata, I. Ieiri, S. Ishiguro, H. Aono, K. Inoue, T. Koide, S. Ohgi, K.Otsubo,Association of pharmacokinetic (CYP2C9) and pharmacodynamic (factors II,VII,IX, and X; proteins S and C; and g-glutamyl carboxylase) gene variants withwarfarin sensitivity. Blood,2004,103;2630–2635.
18. J.Q. He, J. Ruan, J.E. Connett, N.R. Anthonisen, P.D. Pare′PD, A.J. Sandford,Antioxidant gene polymorphisms and susceptibility to a rapid decline in lung functionin smokers. Am. J. Respir. Crit. Care Med,2002,166;323–328.
19. Camenisch U, Naegeli H.Role of DNA repair in the protection against genotoxicstress，EXS.2009;99:111-50。
20. Eker AP, Quayle C, Chaves I, vander Horst GT.DNA repair in mammalian cells:Direct DNA damage reversal: elegant solutions for nasty problems. Cell Mol Life Sci.2009Mar;66(6):968-80.
21. Shrivastav M, De Haro LP, Nickoloff JA.Regulation of DNA double-strand breakrepair pathway choice. Cell Res.2008Jan;18(1):134-47.
22.吴孟超。中华普外科手术学杂志.2009,3,(4);691-694.
23. Mor G, Visintin I, Lai Y, Zhao H, Schwartz P, Rutherford T, et al. Serum proteinmarkers for early detection of ovarian cancer. Proceedings of the National Academyof Sciences of the United States of America.2005;102(21):7677–82.
24. Kim K, Visintin I, Alvero AB, Mor G. Development and validation of a protein-basedsignature for the detection of ovarian cancer. Clinics in Laboratory Medicine.2009;29(1):47–55.
25. De Boer JG Polymorphisms in DNA repair and environmental interactions. MutatRes，2002，509:201–210。
26. Berwick M, Vineis P.Markers of DNA repair and susceptibility to cancer in humans:an epidemiologic review. J Natl Cancer Inst，2000，92:874–897.
27. Kubota Y，Nash RA，Kltmgland A，et al．Reconstitution of DNA base excision repairwith purified human proteins：interaction between DNA polymerase beta and theXRCC1protein[J]．EMBO J，1996，15(23)：6662-6670．
28. R.J. Hung, J. Hall, P. Brennan, P. Boffetta, Genetic polymorphisms in the baseexcision repair pathway and cancer risk: a HuGE review. Am. J. Epidemiol.2005),162(10):925–942.
29. I. Laczmanska, J. Gil, P. Karpinski, A. Stembalska, J. Kozlowska, H. Busza,A.Trusewicz, K. Pesz, D. Ramsey, K. Schlade-Bartusiak, N. Blin, M.M.Sasiadek,Influence of polymorphisms in xenobiotic-metabolizing genes andDNA-repair genes on diepoxybutane-induced SCE. Environ. Mol. Mutagen.2006,47;666–673.
30. Weber C A,Salazar E P,Stewart S A,et aI. ERCC2:cDNA cloning and molecularcharacterization of a human nucleotide excision repair gene with hgh homology toyeast RAD3. EMBO J,1990,9(5):1437。
31. Shen MR, Jones IM, Mohrenweiser H. Nonconservative amino acid substitutionvariants exist at polymorphic frequency in DNA repair genes in healthy humans。Cancer Res.1998Feb15;58(4):604-8.
32. M Felicitas Lopez-Cima,1Patricia Gonzalez-Arriaga,1Laura Garcia-Castro, et aI.Polymorphisms in XPC, XPD, XRCC1, and XRCC3DNA repair genes and lungcancer risk in a population of Northern Spain. BMC Cancer.2007;7:162.
33.杨万水,高静,高姗等，吸烟与肝癌前瞻性研究的荟萃分析。肿瘤2010，30(3)：247－252。
34. Walsh B, Grant M. Public health implications of alcohol production and trade[M].Geneva: WHO,1985.
35.郝伟,杨德森,何鸣.我国饮酒现状、预测及对策[J].中国临床心理学杂志,1995,3：244－245.
36. Parkin DM,Bray F, Ferlay J. Global cancer statistics,2002〔J〕. CA Cancer J Clin,2005,55:74-108.
37.曾运红,谭卫仙.原发性肝癌发病主要危险因素的Meta分析〔J〕.现代预防医学,2004,31(2):172-174.
38. Thomp son LH, Brookman KW, Jones NJ, et al. Molecular cloning of the humanXRCC1gene, which corrects defective DNA strand break repair and sister chromaticexchange [J]. Mol Cell Biol,1990,10(12):6160-6171.
39. Thacker J,Zdzienicka MZ. The mammalian XRCC genes:their roles in DNA repairand genetic stability. DNA Repair,2003,2:655－72.
40. Richard D W. Nucleotide excision repair in mammalian cells. J Biol Chem.1997Sep19;272(38):23465-8。
41. Thornton K，Forstner M，Shen MR，et al．Purification，characterization，andcrystallization of the distal BRCT domain of the human XRCC1DNA repairprotein[J]．Protein Expr Purif，1999，16(2)：236-242．
42. Bork P，Hofmann K，Bucher P，et a1．A superfamily of conserved domains in DNAdamage-responsive cell cycle checkpoint proteins[J]．FASEB J，1997，11(1)：68-76．
43. Wilson SH．Mammalian base excision repair and DNA polymerase beta[J]．MutatRes，1998，407(3)：203-215．
44.．Kubota Y，Nash RA，Kltmgland A，et a1．Reconstitution of DNA base excisionrepair with purified human proteins：interaction between DNA polymerase beta andthe XRCC1protein[J]．EMBO J，1996，15(23)：6662-6670．
45. J.K. Horton, M. Watson, D.F. Stefanick, D.T. Shaughnessy, J.A. Taylor, S.H.Wilson,XRCC1and DNA polymerase β in cellular protection against cytotoxic DNAsingle-strand breaks. Cell Res.2008,18;48–63.
46. O.Mortusewicz, H. Leonhardt, XRCC1and PCNA are loading platforms with distinctkinetic properties and different capacities to respond to multiple DNA lesions. BMCMol. Biol.2007,8;81.
47. L.H. Thompson, M.G. West, XRCC keeps DNA from getting stranded. Mutat. Res.2000,459;1–18.
48. S. Sterpone, R. Cozzi, Influence of XRCC1genetic polymorphisms on ionizingradiation-induced DNA damage and repair. J. Nucleic Acids,2010.
49. S.Z. Abdel-Rahman, A.S. Soliman, M.L. Bondy, S. Omar, S.A. El-Badaway,H.M.Khaled, I.A. Seifeldin, B. Levin, Inheritance of the194Trp and the399Glnvariant alleles of the DNA repair gene XRCC1are associated with increased risk ofthe early-onset colorectal carcinoma in Egypt. Cancer Lett.2000,159;79–86.
50. R.J. Hung, J. Hall, P. Brennan, P. Boffetta, Genetic polymorphisms in the baseexcision repair pathway and cancer risk: a HuGE review. Am. J. Epidemiol.2005),162(10):925–942.
51. I. Laczmanska, J. Gil, P. Karpinski, A. Stembalska, J. Kozlowska, H. Busza,A.Trusewicz, K. Pesz, D. Ramsey, K. Schlade-Bartusiak, N. Blin, M.M.Sasiadek,Influence of polymorphisms in xenobiotic-metabolizing genes andDNA-repair genes on diepoxybutane-induced SCE. Environ. Mol. Mutagen.2006,47;666–673.
52. G. Ji, A. Gu, P. Zhu, Y. Xia, Y. Zhou, F. Hu, L. Song, S. Wang, X. Wang, Joint effectsof XRCC1polymorphisms and polycyclic aromatic hydrocarbons exposure on spermDNA damage and male infertility.Toxicol. Sci.,2010,116;92–98.
53. E.M. Sturgis, E.J. Castillo, L. Li, R. Zheng, A.S. Eicher, G.L. Clayman, S.S. Strom,M.R.Spitz, Q. Wei, Polymorphisms of DNA repair gene XRCC1in squamous cellcarcinoma of the head and neck. Carcinogenesis,1999,20(11):2125–2129.
54. C. Harms, S.A. Salama, C.H. Sierra-Torres, N. Cajas-Salazar, W.W. Au,Polymorphisms in DNA repair genes, chromosome aberrations and lung cancer.Environ.Mol. Mutagen.2004,44;74–82.
55. J.M. Lee, Y.C. Lee, S.Y. Yang, P.W. Yan, S.P. Luh, C.J. Lee, C.J. Chen, M.T. Wu,Genetic polymorphisms of XRCC1and risk of the esophageal cancer. Int. J. Cancer,2001,95;240–246.
56. H. Shen, Y. Xu, Y. Qian, R. Yu, Y. Qin, L. Zhou, L. Wang, X. Wang, M.R. Spitz, Q.Wei,Polymorphisms of the DNA repair gene XRCC1and risk of gastric cancer in aChinese population. Int. J. Cancer,2000,88;601–606.
57. S.Z. Abdel-Rahman, A.S. Soliman, M.L. Bondy, S. Omar, S.A. El-Badaway,H.M.Khaled, I.A. Seifeldin, B. Levin, Inheritance of the194Trp and the399Glnvariant alleles of the DNA repair gene XRCC1are associated with increased risk ofthe early-onset colorectal carcinoma in Egypt. Cancer Lett.2000,159;79–86.
58. Lunn RM, Helzlsouer KJ, Parshad R, Umbach DM, Harris EL, Sanford KK, Bell DA.XPD polymorphisms: effects on DNA repair proficiency。Carcinogenesis.2000Apr;21(4):551-5.
59. Shen MR, Jones IM, Mohrenweiser H. Nonconservative amino acid substitutionvariants exist at polymorphic frequency in DNA repair genes in healthy humans。Cancer Res.1998Feb15;58(4):604-8.
60. Jia Z, Yin Z, Guan P, Zhou B. The Association between Polymorphisms of XPD andSusceptibility of Lung Cancer: A meta Analysis. Zhongguo Fei Ai Za Zhi.2009,12(10):1079-84.
61. Yuan H, Niu YM, Wang RX, Li HZ, Chen N.Association between XPD Lys751Glnpolymorphism and risk of head and neck cancer: a meta-analysis Genet Mol Res.2011Nov22;10(4).---。
62.宋春英，谭文，林东昕．中国DNA修复基因XRCC1单核苷酸多态性及其与食管癌风险的关系[J]．癌症，2001，20(1)：28-31．
63. Lunn RM, Langlois RG, Hsieh LL, et al. XRCC1Polymor-phisms: effects onaflatoxin B12DNA adducts and glycophorin a variant frequency [J]. Cancer Res,1999,59(11):2557-2561.
64. Abdel-Rahman SZ, Soliman AS, Bondly ML, et al. Inheritance of the194Trp andthe399Gln variant alleles of the DNA repair gene XRCC1are associated withincreased risk of early2onset colorectal carcinoma in Egypt [J]. Cancer Let t,2000,159(1):79-86.
65. David-Beabes GL, London SJ. Genetic polymorphism of XRCC1and lung cancerrisk among African2Americans and Caucasians [J]. L ung Cancer,2001,34(3):333-339.
66. Shen MR，Jones IM．Mohrenweiser H．Nonconservative amino acid substitutionvariants exist at polymorphic frequency in DNA repair genes in healthyhumans[J]．Cancer Res，1998，58(4)：604-608．
67.邢德印,齐军,谭文,等.北京地区汉族人群DNA修复基因XPD单核苷酸多态与肺癌及食管癌风险的研究[J].中华医学遗传学杂志,2003,20(1):35-38.
68.梁刚,程家蓉,张学宏,等. DNA修复基因XPD单核苷酸多态与胆道癌遗传易感性[J].肿瘤,2006,26(5):444-449.
69. Butkiewicz D, Rusin M, Enewold L，et al. Genetic polymorphisms in DNA repairgenes and risk of lung cancer. Carcinogenesis.2001r;22(4):593-7.
70.叶家才，崔书中，巴明臣。原发性肝癌的流行病学特征及其危险因素。实用医学杂志2008，24(10)：1839-1841.
71.陈建国,朱健,张永辉,等.江苏省启东地区1973至2002年肝癌发病率长期趋势的评价[J].中华医学杂志,2005,85(43):3052-3056.
72. E1-Serag H B. Epidemiology of hepatocellular carcinoma [J]. Clin LiverDis,2001(5):87-107.
73. Angeline S.Andrew1, Heather H.Nelson, Karl T.Kelsey,. Concordance of multipleanalytical approaches demonstrates a complex relationship between DNA repair geneSNPs, smoking and bladder cancer susceptibility. Carcinogenesis,2006,27(5);1030–1037.
74. Rybarova S, Vecanova J, Hodorova I, et al.Association between polymorphisms ofXRCC1, p53and MDR1genes, the expression of their protein products andprognostic significance in human breast cancer. Med Sci Monit.2011,17(12):354-363.
75. Yu MW, Yang SY, Pan IJ, et al. Polymorphisms in XRCC1and glutathioneS2transferase genes and hepatitis B－related hepatocellular carcinoma [J]. J NatCancer Inst,2003,95(19):1485-1488.
76.孙晓艳，王炳元．饮酒与肝癌[J]．现代医药卫生，2007，23(7)：1007-1008．
77. Yin G, Morita M, Ohnaka K, Toyomura K, et al. Genetic Polymorphisms of XRCC1,Alcohol Consumption, and the Risk of Colorectal Cancer in Japan. J Epidemiol.2012;22(1):64-71。
78. Stern MC, Siegmund KD, Conti DV, Corral R, Haile RW. XRCC1, XRCC3, and XPDpolymorphisms as modifiers of the effect of smoking and alcohol on colorectaladenoma risk. Cancer Epidemiol Biomarkers Prev.2006Dec;15(12):2384-90.
79. Rayjean J，Hung，Janet Hall，et al．Genetic polymorphisms in the base excision repairpathway and cancer risk：A HuGE review[J]．American Journal Epidemiology，2005，162：925-942．
80. Hou SM, F lt S, Angelini S, et al．The XPD variant alleles are associated withincreased aromatic DNA adduct level and lung cancer risk. Carcinogenesis.2002Apr;23(4):599-603.
81.汤伯明,张竹梅,王其军,等.饮酒与肝癌的病例对照研究〔J〕.实用肿瘤学杂志,2002,16(2):88-91.
82. Teufel A，Staib F，Kanzler S，et a1．Genetics of Hepatocellular Carcinoma[J]．WorldJ Gastroenterol，2007，28：13(16)：2271-2282．
83. Manjula Kiran，Roli Saxena， Yogesh K. Chawla，et al．Polymorphism of DNArepair gene XRCC1and hepatitis-related hepatocellular carcinoma risk in Indianpopulation.Mol Cell Biochem (2009)327:7–13.
84. Zeng XY, Qiu XQ, Ji L, et al．Study on the relationship between hepatocellularcarcinoma and the interaction between polymorphisms in DNA repair gene XPD andenvironmental factors. Zhonghua Liu Xing Bing Xue Za Zhi.2009Jul;30(7):702-5.
85. Libin Jia,XinWeiWang,Curtis C. Hepatitis B virus X protein does not influenceessential steps of nucleotide excision repair effected by human liver extracts.Biochem Biophys Res Commun.2003Dec19;312(3):806-10.
86. Turati F, Edefonti V, Talamini R, et al． Family history of liver cancer andhepatocellular carcinoma.2011Nov16. doi:10.1002/hep.24794.
87. Falagan-Lotsch P, Rodrigues MS, Esteves V, et al．XRCC1gene polymorphisms in apopulation sample and in women with a family history of breast cancer from Rio deJaneiro (Brazil). Genet Mol Biol.2009;32(2):255-9.
88. Yousry Mostafa Hussien Amal F. Gharib Hanan A. Awad Rehab A. Karam WaelH. Elsawy. Impact of DNA repair genes polymorphism (XPD and XRCC1)on the riskof breast cancer in Egyptian female patients.
89. L Cheng,M R Spitz,W K Hong,et aI. Reduced expression levels of nucleotideexcision repair genes in lung cancer. Carcinogenesis,2000,21:1527
90. Ulla Voget,Bjorn A,Nexo,et al. ERCCl,XPD and RAl mRNA Ievels inlymphocyles arenot associated with lung cancer risk a prospective study ofDaries.Mutation Res,2006,59(3):88
91. Calandra T, Roger T. Macrophage migration inhibitory factor: a regulator of innateimmunity.Nature Reviews Immunology.2003;3(10):791–800.
92. Simons D, Grieb G, Hristov M, Pallua N, Weber C, Bernhagen J, et al.Hypoxia-induced endothelial secretion of macrophage migration inhibitory factor androle in endothelial progenitor cell recruitment. J Cell Mol Med.2010Epub ahead ofprint.
93. Calandra T, Bernhagen J, Mitchell RA, Bucala R. The macrophage is an importantand previously unrecognized source of macrophage migration inhibitory factor.Journal of Experimental.Medicine.1994;179(6):1895–902.
94. Mitchell RA, Metz CN, Peng T, Bucala R. Sustained mitogen-activated protein kinase(MAPK) and cytoplasmic phospholipase A2activation by macrophage migrationinhibitory factor (MIF).Regulatory role in cell proliferation and glucocorticoid action.Journal of Biological Chemistry.1999;274(25):18100–6.
95. Noh SU, Park YM. The effect of green tea polyphenols on macrophage migrationinhibitory factor-associated steroid resistance.Br J Dermatol.2011Nov4. doi:
10.1111/j.1365-2133.2011.10720.
96. Kofoed K, Andersen O, Kronborg G, Tvede M, Petersen J, Eugen-Olsen J, et al. Useof plasma C-reactive protein, procalcitonin, neutrophils, macrophage migrationinhibitory factor, soluble urokinase-type plasminogen activator receptor, and solubletriggering receptor expressed on myeloid cells-1in combination to diagnoseinfections: a prospective study. Critical Care (London, England).2007;11(2):R38.
97. Bruchfeld A, Carrero JJ, Qureshi AR, Lindholm B, Barany P, Heimburger O, et al.Elevated serum macrophage migration inhibitory factor (MIF) concentrations inchronic kidney disease (CKD) are associated with markers of oxidative stress andendothelial activation. Molecular Medicine.2009;15(3-4):70–5.
98. Chesney J, Metz C, Bacher M, Peng T, Meinhardt A, Bucala R. An essential role formacrophage migration inhibitory factor (MIF) in angiogenesis and the growth of amurine lymphoma.Molecular Medicine.1999;5(3):181–91.
99. Bucala R, Donnelly SC. Macrophage migration inhibitory factor: a probable linkbetween inflammation and cancer. Immunity.2007;26(3):281–5.
100. Hawkins O, Verma B, Lightfoot S, et al. An HLA-presented fragment of macrophagemigration inhibitory factor is a therapeutic target for invasive breast cancer. JImmunol.2011;186(11):6607-16.
101. Shimizu T, Abe R, Nakamura H, Ohkawara A, Suzuki M, Nishihira J. High expressionof macrophage migration inhibitory factor in human melanoma cells and its role intumor cell growth and angiogenesis. Biochemical&Biophysical ResearchCommunications.1999;264(3):751–8.
102. Hudson JD, Shoaibi MA, Maestro R, Carnero A, Hannon GJ, Beach DH. Aproinflammatory cytokine inhibits p53tumor suppressor activity. Journal ofExperimental Medicine.1999;190(10):1375–82.
103. Mor G, Visintin I, Lai Y, Zhao H, Schwartz P, Rutherford T, et al. Serum proteinmarkers for early detection of ovarian cancer. Proceedings of the National Academyof Sciences of the United States of America.2005;102(21):7677–82.
104. Kim K, Visintin I, Alvero AB, Mor G. Development and validation of a protein-basedsignature for the detection of ovarian cancer. Clinics in Laboratory Medicine.2009;29(1):47–55.
105. Shun CT, Lin JT, Huang SP, Lin MT, Wu MS. Expression of macrophage migrationinhibitory factor is associated with enhanced angiogenesis and advanced stage ingastric carcinomas. World Journal of Gastroenterology.2005;11(24):3767–71.
106. Camlica H, Duranyildiz D, Oguz H, Oral EN, Yasasever V. The diagnostic value ofmacrophage migration inhibitory factor (MIF) in gastric cancer. Pathology OncologyResearch.2008;14(1):79–83.
107. Mohri Y, Mohri T, Wei W, Qi YJ, Martin A, Miki C, et al. Identification ofmacrophage migration inhibitory factor and human neutrophil peptides1-3aspotential biomarkers for gastric cancer. British Journal of Cancer.2009;101(2):295–302.
108. Yasasever V, Camlica H, Duranyildiz D, Oguz H, Tas F, Dalay N. Macrophagemigration inhibitory factor in cancer. Cancer Investigation.2007;25(8):715–9.
109. Baugh JA, Chitnis S, Donnelly SC, Monteiro J, Lin X, Plant BJ, et al. A functionalpromoter polymorphism in the macrophage migration inhibitory factor (MIF) geneassociated with disease severity in rheumatoid arthritis. Genes&Immunity.2002;3(3):170–6.
110. Radstake TR, Sweep FC, Welsing P, Franke B, Vermeulen SH, Geurts-Moespot A, etal. Correlation of rheumatoid arthritis severity with the genetic functional variants andcirculating levels of macrophage migration inhibitory factor. Arthritis&Rheumatism.2005;52(10):3020–9.
111. Arisawa T, Tahara T, Shibata T, Nagasaka M, Nakamura M, Kamiya Y, et al.Functional promoter polymorphisms of the macrophage migration inhibitory factorgene in gastric carcinogenesis. Oncology Reports.2008;19(1):223–8.
112. Meyer-Siegler KL, Vera PL, Iczkowski KA, Bifulco C, Lee A, Gregersen PK, et al.Macrophage migration inhibitory factor (MIF) gene polymorphisms are associatedwith increased prostate cancer incidence. Genes&Immunity.2007;8(8):646–52.
113. Morand EF, Leech M, Bernhagen J． MIF a new cytokine link between rheumatoidarthritis and atherosclerosis J.Nature Reviews Drug Discov2005,5399－411．
114.柳爱华，石梅，赵勤等。MIF基因启动子多态性与结核病相关性研究进展。热带医学杂志2010年9月第10卷第9期。
115. Coussens LM, Werb Z. Inflammation and cancer. Nature.2002Dec19-26;420(6917):860-7.
116. Kuper H, Adami HO, Trichopoulos D. Infections as a major preventable cause ofhuman cancer. Journal of Internal Medicine.2000;248(3):171–83.
117. Balkwill F, Mantovani A. Inflammation and cancer: back to Virchow? Lancet.2001;357(9255):539–45.
118. Bucala R, Donnelly SC. Macrophage migration inhibitory factor: a probable linkbetween inflammation and cancer. Immunity.2007;26(3):281–5.
119.邓玮,易永芬,闫田静等，胃癌组织和细胞中P115、M IF的表达及意义。第三军医大学学报。2011；33(3)：241-245。
120.李虎,梁朝朝,郝宗耀等。M IF在前列腺癌组织中的表达及其意义[J].安徽医药,2009；13(11)：1361-1363。
121. Han Y, Zhang C. Macrophage migration inhibitory factor plays a pivotal role inhepatocellular carcinoma and may be a noninvasive imaging target. Med Hypotheses.2010;75(6):530-2.
122. Eiji H，Takashi O，Dipok KD,et a1．Overexpression of macmphage migrationinhibitory factor induces angiogenesis and deteriorates prognosis after radicalresection for hepatocelular carcinoma. Cancer，2005，103：588—596．
123. Donn R，Alourfi Z，De Benedetti F，et a1．Mutation screening of the macrophagemigration inhibitory factor gene：positive association of a functional polymorphism ofmacrophage migration inhibitory factor with juvenile idiopathic arthritis．ArthritisRheum，2002，46：2402-2469．
124. Xia HH, Zhang ST, Lam SK, Lin MC, Kung HF, Wong BC. Expression ofmacrophage migration inhibitory factor in esophageal squamous cell carcinoma andeffects of bile acids and NSAIDs. Carcinogenesis.2005Jan;26(1):11-5.
125. Ren Y, Law S, Huang X, Lee PY, Bacher M, Srivastava G, Wong J. Macrophagemigration inhibitory factor stimulates angiogenic factor expression and correlateswith differentiation and lymph node status in patients with esophageal squamous cellcarcinoma. Ann Surg.2005Jul;242(1):55-63.
126. Omuro, A.M., Delattre, J.Y., What is the place of bevacizumab and irinotecan in thetreatment of glioblastoma and other malignant gliomas? Curr. Opin. Neurol.2008.21,717–719.
127. Sachdev, J.C., Jahanzeb, M., Evolution of bevacizumab-based therapy in themanagement of breast cancer. Clin. Breast Cancer2008.8,402–410.
128. De Benedetti F, Meazza C, Vivarelli M, Rossi F, Pistorio A, Lamb R, et al. Functionaland prognostic relevance of the173polymorphism of the macrophage migrationinhibitory factor gene in systemic-onset juvenile idiopathic arthritis. Arthritis&Rheumatism.2003;48(5):1398–407.
129. Mizue Y, Ghani S, Leng L, McDonald C, Kong P, Baugh J, et al. Role for macrophagemigration inhibitory factor in asthma. Proceedings of the National Academy ofSciences of the United States of America.2005;102(40):14410–5.
130. Wu J, Fu S, Ren X, Jin Y, Huang X, Zhang X, et al. Association of MIF promoterpolymorphisms with childhood asthma in a northeastern Chinese population. TissueAntigens.2009;73(4):302–6.
131. Nohara H, Okayama N, Inoue N, Koike Y, Fujimura K, Suehiro Y, et al. Associationof the173G/C polymorphism of the macrophage migration inhibitory factor genewith ulcerative colitis. Journal of Gastroenterology.2004;39(3):242–6.
132. Donn RP, Plant D, Jury F, Richards HL, Worthington J, Ray DW, et al. Macrophagemigration inhibitory factor gene polymorphism is associated with psoriasis. Journal ofInvestigative Dermatology.2004;123(3):484–7.
133. McDevitt MA, Xie J, Shanmugasundaram G, Griffith J, Liu A, McDonald C, et al. Acritical role for the host mediator macrophage migration inhibitory factor in thepathogenesis of malarial anemia. Journal of Experimental Medicine.2006;203(5):1185–96.
134. Zhong XB, Leng L, Beitin A, Chen R, McDonald C, Hsiao B, et al. Simultaneousdetection of microsatellite repeats and SNPs in the macrophage migration inhibitoryfactor (MIF) gene by thin-film biosensor chips and application to rural field studies.Nucleic Acids Research.2005;33(13):e121.
135. Farinati F, Rinaldi M, Gianni S, et al. How should patients with hepatocellularcarcinoma be staged? Validation of a new prognostic system[J]. Cancer,2000,89(11):2266。
136. Seki T, Tamai T, Nakagawa T, et al. Combination therapy with transcathter arterialchemoembolization and percutaneous microwave coagulation therapy forhepatocellular carcinoma Cancer,2000,89(6):1245。
1. I.Berlin,B.deBrettes,G.Aymard,B.Diquet,L.Arnulf,A.J.Puech.Dopaminergic drugresponse and the genotype(Taq IA polymorphism)of the dopamine D2receptor.Int.J.Neuropsychopharmacol,2000,3;35–43.
2. I. Ieiri, H. Takane, T. Hirota, K. Otsubo, S. Higuchi, Genetic polymorphisms of drugtransporters: pharmacokinetic and pharmacodynamic consequences in pharmacotherapy.Expert Opin. Drug Metab. Toxicol.2006,2;651–674.
3. E. Shikata, I. Ieiri, S. Ishiguro, H. Aono, K. Inoue, T. Koide, S. Ohgi, K.Otsubo,Association of pharmacokinetic (CYP2C9) and pharmacodynamic (factors II,VII,IX, and X; proteins S and C; and g-glutamyl carboxylase) gene variants withwarfarin sensitivity. Blood,2004,103;2630–2635.
4. J.Q. He, J. Ruan, J.E. Connett, N.R. Anthonisen, P.D. Pare′, A.J. Sandford, Antioxidantgene polymorphisms and susceptibility to a rapid decline in lung function in smokers.Am. J. Respir. Crit. Care Med,2002,166;323–328.
5. J.K. Horton, M. Watson, D.F. Stefanick, D.T. Shaughnessy, J.A. Taylor, S.H.Wilson,XRCC1and DNA polymerase β in cellular protection against cytotoxic DNAsingle-strand breaks. Cell Res.2008),18;48–63.
6. O. Mortusewicz, H. Leonhardt, XRCC1and PCNA are loading platforms with distinctkinetic properties and different capacities to respond to multiple DNA lesions. BMC Mol.Biol.2007,8;81.
7. L.H. Thompson, M.G. West, XRCC keeps DNA from getting stranded. Mutat. Res.2000),459;1–18.
8. S. Sterpone, R. Cozzi, Influence of XRCC1genetic polymorphisms on ionizingradiation-induced DNA damage and repair. J. Nucleic Acids,2010.
9. R.S. Tebbs, M.L. Flannery, J.J. Meneses, A. Hartmann, J.D. Tucker, L.H. Thompson,J.E.Cleaver, R.A. Pedersen, Requirement for the XRCC1DNA base excision repair geneduring early mouse development. Dev. Biol.1999,208;513–529.
10. L.H. Thompson, K.W. Brookman, L.E. Dillehay, A.V. Carrano, J.A. Mazrimas,C.L.Mooney, J.L. Minkler, A CHO-cell strain having hypersensitivity to mutagens, adefect in DNA strand-break repair, and an extraordinary baseline frequency of sisterchromatid exchange. Mutat. Res.1982,95(2–3):427–440.
11. L.H. Thompson, K.W. Brookman, N.J. Jones, S.A. Allen, A.V. Carrano, Molecularcloning of the human XRCC1gene, which corrects defective DNA strand break repairand sister chromatid exchange. Mol. Cell. Biol.1990),10(12):6160–6171.
12. R.S. Tebbs, M.L. Flannery, J.J. Meneses, A. Hartmann, J.D. Tucker, L.H. Thompson,J.E.Cleaver, R.A. Pedersen, Requirement for the XRCC1DNA base excision repair geneduring early mouse development. Dev. Biol.1999,208;513–529.
13. R.J. Hung, J. Hall, P. Brennan, P. Boffetta, Genetic polymorphisms in the base excisionrepair pathway and cancer risk: a HuGE review. Am. J. Epidemiol.2005),162(10):925–942.
14. I. Laczmanska, J. Gil, P. Karpinski, A. Stembalska, J. Kozlowska, H. Busza,A.Trusewicz, K. Pesz, D. Ramsey, K. Schlade-Bartusiak, N. Blin, M.M.Sasiadek,Influence of polymorphisms in xenobiotic-metabolizing genes and DNA-repairgenes on diepoxybutane-induced SCE. Environ. Mol. Mutagen.2006,47;666–673.
15. S.Z. Abdel-Rahman, R.A. El-Zein, The399Gln polymorphism in the DNA repair geneXRCC1modulates the genotoxic response induced in human lymphocytes by thetobacco-specific nitrosamine NNK. Cancer Lett.2000,159;63–71.
16. Y. Wang, M.R. Spitz, Y. Zhu, Q. Dong, S. Shete, X. Wu, From genotype to phenotype:correlating XRCC1polymorphisms with mutagen sensitivity. DNA Repair2003,2;901–908.
17. S. Angelini, R. Kumar, F. Carbone, J.L. Bermejo, F. Maffei, G. Cantelli-Forti, K.Hemminki, P. Hrelia, Inherited susceptibility to bleomycin-induced micronuclei:correlatingpolymorphisms in GSTT1, GSTM1and DNA repair genes with mutagen sensitivity.Mutat. Res.2008),638(1–2):90–97.
18. Y. Li, M.J. Marion, J. Zipprich, G. Freyer, R.M. Santella, C. Kanki, P.W.Brandt-Rauf,The role of XRCC1polymorphisms in base excision repair of etheno-DNAadducts in French vinyl chloride workers. Int. J. Occup. Med. Environ. Health,2006,19(1):45–52.
19. P. Vodicka, R. Kumar, R. Stetina, S. Sanyal, P. Soucek, V. Haufroid, M. Dusinska,M.Kuricova, M. Zamecnikova, L. Musak, J. Buchancova, H. Norppa, A. Hirvonen,L.Vodickova, A. Naccarati, Z.Matousu, K.Hemminki, Genetic polymorphisms in DNArepair genes and possible links with DNA repair rates, chromosomal aberrations andsingle strand breaks in DNA. Carcinogenesis,2004),25(5):757–763.
20. W.W. Au, S.A. Salama, C.H. Sierra-Torres, Functional characterization of polymorphisms in DNA repair genes using cytogenetic challenge assays, Environ.Health Perspect.2003,111;1843–1850.
21. S. Marsin, A.E. Vidal, M. Sossou, J. Me′nissier-de Murcia, F. Le Page, S. Boiteux, G.deMurcia, J.P. Radicella, Role of XRCC1in the coordination and stimulation of oxidativeDNA damage repair initiated by the DNA glycosylase hOGG1. J. Biol.Chem.2003,278(45):44068–44074.
22. P. Vodicka, R. Kumar, R. Stetina, S. Sanyal, P. Soucek, V. Haufroid, M. Dusinska,M.Kuricova, M. Zamecnikova, L. Musak, J. Buchancova, H. Norppa, A. Hirvonen,L.Vodickova, A. Naccarati, Z.Matousu, K.Hemminki, Genetic polymorphisms in DNArepair genes and possible links with DNA repair rates, chromosomal aberrations andsingle-strand breaks in DNA. Carcinogenesis,2004,25(5):757–763.
23. A.R. Collins, M. Dusinska′, E. Horva′thova′, E. Munro, M. Savio, R. Ste tina,Interindividual differences in repair of DNA base oxidation. Measured in vitro with thecomet assay. Mutagenesis,2001,16(4):297–301.
24. J. Slyskova, M. Dusinska, M. Kuricova, P. Soucek, L. Vodickova, S. Susova,A.Naccarati, E. Tulupova, P. Vodicka, Relationship between the capacity to repair8-oxoguanine biomarkers of genotoxicity and individual susceptibility in styreneexposedworkers. Mutat. Res.2007,634;101–111.
25. J. Tuimala, G. Szekely, S. Gundy, A. Hirvonen, H. Norppa, Genetic polymorphisms ofDNA repair and xenobiotic-metabolizing enzymes: role in mutagen sensitivity.Carcinogenesis,2002),23(6):1003–1008.
26. B. Hao, X. Miao, Y. Li, X. Zhang, T. Sun, G. Liang, Y. Zhao, Y. Zhou, H. Wang, X.Chen,L. Zhang, W. Tan, Q. Wei, D. Lin, F. He, A novel T-77C polymorphism in DNArepair gene XRCC1contributes to diminished promoter activity and increased risk ofnon-small cell lung cancer. Oncogene,2006,25:3613–3620.
27. L. Liu, P. Yuan, L. Liu, C. Wu, X. Zhang, H. Guo, R. Zhong, Y. Xu, J. Wu, S. Duan,R.Rui, T. Wu, S. Nie, X. Miao, D. Lin, A functional-77T→C polymorphism in XRCC1is associated with risk of breast cancer. Breast Cancer Res. Treat.2010, June13
28. P. Mohamadynejad, M. Saadat, Genetic polymorphisms of XRCC1(at codons194and399) in Shiraz population (Fars Province, Southern Iran). Mol. Biol. Rep.2007,September14。
29. N.A. Kocabas, B. Karahalil, XRCC1Arg399Gln genetic polymorphism in a Turkishpopulation. Int. J. Toxicol.2006,25;419–422.
30. S. Sterpone, V. Mastellone, L. Padua, F. Novelli, C. Patrono, T. Cornetta,D.Giammarino, V. Donato, A. Testa, R. Cozzi, Single-nucleotide polymorphisms in BERand HRR genes. XRCC1haplotypes and breast cancer risk in Caucasian women.J.Cancer Res. Clin. Oncol.2010,136;631–636.
31. R. Brem, D.G. Cox, B. Chapot, N. Moullan, P. Romestaing, J.P. Ge′rard, P. Pisani,J.Hall, The XRCC1-77T> C variant: haplotypes, breast cancer risk, response toradiotherapy and the cellular response to DNA damage. Carcinogenesis,2006,27;2469–2474.
32. R.M. Lunn, R.G. Langlois, L.L. Hsieh, C.L. Thompson, D.A. Bell, XRCC1polymorphisms:effects on aflatoxin B1–DNA adducts and gylcophorin A variantfrequency.Cancer Res,1999,59;2557–2561.
33. E.J. Duell, J.K. Wiencke, T.J. Cheng, A. Varkonyi, Z.F. Zuo, T.D. Ashok, J.E. Mark,J.C.Wain, D.C. Christiani, K.T. Kelsey, Polymorphism in the DNA repair genes XRCC1and ERCC2and biomarkers of DNA damage in human blood mononuclearcells.Carcinogenesis,2000,21;965–971.
34. G. Matullo, D. Palli, M. Peluso, S. Guarrera, S. Carturan, E. Celentano, V. Krogh,A.Munnia, R. Tumino, S. Polidoro, A. Piazza, P. Vineis, XRCC1, XRCC3, XPD genepolymorphisms. Smoking and32P–DNA adducts in a sample of healthysubjects.Carcinogenesis,2001,22(9):1437–1445.
35. G. Ji, A. Gu, P. Zhu, Y. Xia, Y. Zhou, F. Hu, L. Song, S. Wang, X. Wang, Joint effects ofXRCC1polymorphisms and polycyclic aromatic hydrocarbons exposure on sperm DNAdamage and male infertility.Toxicol. Sci.,2010,116;92–98.
36. D. Palli, A. Russo, G. Masala, C. Saieva, S. Guarrera, S. Carturan, A. Munnia,G.Matullo, M. Peluso, DNA adducts levels and DNA repair polymorphisms intraffic-exposed workers and a general population sample.Int,J. Cancer,2001,94;121–127.
37. M. Kuricova, A. Naccarati, R. Kumar, M. Koskinen, S. Sanyal, M. Dusinska, J.Tulinska,L. Vodickova, A. Liskova, E. Jahnova, L. Fuortes, V. Haufroid, K. Hemminki,P. Vodicka,DNA repair and cyclin D1polymorphisms and styreneinduced genotoxicity andimmunotoxicity, Toxicol. Appl. Pharmacol,2005,207; S302–S309.
38. P. Vodicka, R. Kumar, R. Stetina, L. Musak, P. Soucek, V. Haufroid, M. Sasiadek,L.Vodickova, A. Naccarati, J. Sedikova, S. Sanyal, M. Kuricova, V. Brsiak, H. Norppa,J.Buchancova, K. Hemminki, Markers of individual susceptibility and DNA repair rate inworkers exposed to xenobiotics in a tire plant.Environ.Mol. Mutagen,2004,44;283–292.
39. Q. Wang, A.H. Wang, H.S. Tan, N.N. Feng, Y.J. Ye, X.Q. Feng, G. Liu, Y.X. Zheng,Z.L.Xia, Genetic polymorphisms of DNA repair genes and chromosomal damage in workersexposed to1,3-butadiene. Carcinogenesis,2010,31;858–863.
40. Q. Wang, F. Ji, Y. Sun, Y.L. Qiu, W. Wang, F. Wu, W.B. Miao, Y. Li, P.W.Brandt-Rauf,Z.L. Xia, Genetic polymorphisms of XRCC1, HOGG1and MGMT andmicronucleus occurrence in Chinese vinyl chloride-exposed workers. Carcinogenesis,2010,31;1068–1073.
41. N.K. Bolegenova, B.O. Bekmanov, L.B. Djansugurova, R.I. Bersimbaev, S.A.Salama,W.W. Au, Genetic polymorphisms and expression of minisatellite mutations in a3generation population around the Semipalatinsk nuclear explosion test site,Kazakhstan,Int. J. Hyg. Environ. Health,2009,212;654–660.
42. R. Pastorelli, A. Cerri, M. Mezzetti, E. Consonni, L. Airoldi, Effect of DNA repair genepolymorphisms on BPDE–DNA adducts in human lymphocytes. Int. J.Cancer,(2002,100;9–13.
43. J. Shen, M.D. Gammon, M.B. Terry, L. Wang, Q. Wang, F. Zhang, S.L. Teitelbaum,S.M.Eng, S.K. Sagiv, M.M. Gaudet, A.I. Neugut, R.M. Santella, Polymorphisms in XRCC1modify the association between polycyclic aromatic hydrocarbon–DNA adducts,cigarette smoking, dietary antioxidants, and breast cancer risk. Cancer Epidemiol.Biomark. Prev,2005,14(2):336–342.
44. G. Matullo, S. Guarrera, S. Carturan, M. Peluso, C. Malaveille, L. Davico, A. Piazza,P.Vineis, DNA repair gene polymorphisms, bulky DNA adducts in white blood cells andbladder cancer in a case–control study. Int. J. Cancer.2002,92;562–567.
45. Z. Hu, H. Ma, F. Chen, Q. Wei, H. Shen, XRCC1polymorphisms and cancer risk: ameta-analysis of38case–control studies. Cancer Epidemiol. Biomark. Prev.2005,14(7):1810–1818.
46. E.M. Sturgis, E.J. Castillo, L. Li, R. Zheng, A.S. Eicher, G.L. Clayman, S.S. Strom,M.R.Spitz, Q. Wei, Polymorphisms of DNA repair gene XRCC1in squamous cellcarcinoma of the head and neck. Carcinogenesis,1999,20(11):2125–2129.
47. J.M. Lee, Y.C. Lee, S.Y. Yang, P.W. Yan, S.P. Luh, C.J. Lee, C.J. Chen, M.T. Wu,Genetic polymorphisms of XRCC1and risk of the esophageal cancer. Int. J. Cancer,2001,95;240–246.
48. H. Shen, Y. Xu, Y. Qian, R. Yu, Y. Qin, L. Zhou, L. Wang, X. Wang, M.R. Spitz, Q.Wei,Polymorphisms of the DNA repair gene XRCC1and risk of gastric cancer in aChinese population. Int. J. Cancer,2000,88;601–606.
49. S.Z. Abdel-Rahman, A.S. Soliman, M.L. Bondy, S. Omar, S.A. El-Badaway,H.M.Khaled, I.A. Seifeldin, B. Levin, Inheritance of the194Trp and the399Gln variantalleles of the DNA repair gene XRCC1are associated with increased risk of theearly-onset colorectal carcinoma in Egypt. Cancer Lett.2000,159;79–86.
50. C. Wang, Y. Sun, R. Han, XRCC1genetic polymorphisms and bladder cancersusceptibility: a meta-analysis. Urology,2008.
51. T.B. Tumer, D. Yilmaz, C. Tanrikut, G. Sahin, G. Ulusoy, E. Arinc, DNA repair XRCC1Arg399Gln polymorphism alone, and in combination with CYP2E1polymorphismssignificantly contribute to the risk of development of childhood acute lymphoblasticleukemia. Leuk. Res.2010,34;1275–1281.
52. A.H. Gu, J. Lian, N.X. Lu, Y.K. Xia, C.C. Lu, L. Song, S.H. Wang, X.R.Wang,Association of XRCC1gene polymorphisms with idiopathic azoospermia in aChinese population. Asian J. Androl.2007,9(6):781–786.
53. P.L. Chen, K.T. Yeh, Y.Y. Tsai, H. Koeh, Y.L. Liu, H. Lee, Y.W. Cheng, XRCC1, but notAPE1and hOGG1gene polymorphisms is a risk factor for pterygium. Mol. Vis.2010,16;991–996.
54. K. Metsola, V. Kataja, P. Sillanpa¨a¨, P. Siivola, L. Heikinheimo, M. Eskelinen,V.M.Kosma, M. Uusitupa, A. Hirvonen, XRCC1and XPD genetic polymorphisms,smoking and breast cancer risk in a Finnish case–control study. Breast Cancer Res.2005,7(6); R987–R997.
55. B. Thyagarajan, K.E. Anderson, A.R. Folsom, D.R. Jacobs Jr., C.F. Lynch, A. Bargaje,W.Khaliq, M.D. Gross, No association between XRCC1and XRCC3gene polymorphismsand breast cancer risk: Iowa Women’s Health Study. Cancer Detect.Prev.2006,30(4):313–321.
56. A.V. Patel, E.E. Calle, A.L. Pavluck, H.S. Feigelson, M.J. Thun, C. Rodriguez, Aprospective study of XRCC1(X-ray cross-complementing group1) polymorphisms andbreast cancer risk. Breast Cancer Res.2005,7(6): R1168–R1173.
57. S.N. Silva, R. Moita, A.P. Azevedo, R. Gouveia, I. Manita, J.E. Pina, J. Rueff, J.Gaspar,Menopausal age and XRCC1gene polymorphisms: role in breast cancerrisk.Cancer Detect. Prev.2007,31(4):303–309.
58. Y. Zhang, P.A. Newcomb, K.M. Egan, L. Titus-Ernstoff, S. Chanock, R. Welch,L.A.Brinton, J. Lissowska, A. Bardin-Mikolajczak, B. Peplonska, N. Szeszenia-Dabrowska,W. Zatonski, M. Garcia-Closas, Genetic polymorphisms in base-excisionrepair pathway genes and risk of breast cancer. Cancer Epidemiol. Biomark. Prev.2006,15(2):353–358.
59.The Breast Cancer Association Consortium, Commonly studied single-nucleotidepolymorphisms and breast cancer: results from The Breast Cancer AssociationConsortium. J. Natl. Cancer Inst.2006,98(19):1382–1396.
60. H. Li, T.C. Ha, B.C. Tai, XRCC1gene polymorphisms and breast cancer risk indifferent populations: a meta analysis. Breast,2009,18:183–191.
61. D. Butkiewicz, M. Rusin, L. Enewold, P.G. Shields, M. Chorazy, C.C. Harris, Geneticpolymorphisms in DNA repair genes and risk of lung cancer. Carcinogenesis,2001,22;593–597.
62. C. Harms, S.A. Salama, C.H. Sierra-Torres, N. Cajas-Salazar, W.W. Au, Polymorphismsin DNA repair genes, chromosome aberrations and lung cancer. Environ.Mol. Mutagen.2004,44;74–82.
63. D. Ratnasinghe, S.X. Yao, J.A. Tangrea, Y.L. Qiao, M.R. Anderson, M.J. Barrett,C.A.Giffen, Y. Erozan, M.S. Tockman, P.R. Taylor, Polymorphisms of the DNA repairgene XRCC1and lung cancer risk. Cancer Epidemiol. Biomark. Prev.2001,10(2);119–123.
64. G.L. David-Beabes, S.J. London, Genetic polymorphisms of XRCC1and lung cancerrisk among African-Americans and Caucasians. Lung Cancer,2001,34333–339.
65. R.J. Hung, P. Brennan, F. Canzian, N. Szeszenia-Dabrowska, D. Zaride, J. Lissowska,P.Rudnai, E. Fabianova, D. Mates, L. Foretova, V. Janout, V. Bencko, A. Chabrier, S.Borel,J. Hall, P. Boffetta, Large-scale investigation of base excision repair geneticpolymorphisms and lung cancer risk in a multicenter study. J. Natl. Cancer Inst.2005,97;56–76.
66. K.K. Divine, F.D. Gilliland, R.E. Crowell, C.A. Stidley, T.J. Bocklage, D.L. Cook,S.A.Belinsky, The XRCC1399glutamine allele is a risk factor for adenocarcinoma ofthe lung, Mutat. Res.2001,273–278.
67. J.Y. Park, S.Y. Lee, H.S. Jeon, N.C. Bae, S.C. Chae, S. Joo, C.H. Kim, J.H. Park, S.Kam,S.I. Kim, T.H. Jung, Polymorphism of the DNA repair gene XRCC1and risk ofprimary lung cancer. Cancer Epidemiol. Biomark. Prev.2002,11;23–27.
68. C. Kiyohara, K. Takayama, Y. Nakanishi, Association of genetic polymorphisms in thebase excision repair pathway with lung cancer risk: a meta-analysis. Lung Cancer,2006,54(3):267–283.
69. J. Schneider, V. Classen, S. Helmig, XRCC1polymorphism and lung cancer risk.ExpertRev. Mol. Diagn.2008,8;761–780.
70. J.D. Figueroa, N. Malats, F.X. Real, D. Silverman, M. Kogevinas, S. Chanock, R.Welch,M. Dosemeci, A. Tardon, C. Serra, A. Carrato, R. Garcia-Closas, G.C. Vinyals,N.Rothman, M. Garcia Clonas, Genetic variation in the base excision repair pathway andbladder cancer risk. Hum. Genet.2007,121;233–242.
71. S.C. Sak, J.H. Barrett, A.B. Paul, D.T. Bishop, A.E. Kiltie, DNA repair gene XRCC1polymorphisms and bladder cancer risk. BMC Genet.2007,8;13.
72. M.J. Felini, A.F. Oslhan, J.C. Schroeder, K.E. North, S.E. Carozza, K.T. Kelsey, M.Liu,T. Rice, J.K. Wiencke, M.R. Wrensch, DNA repair polymorphisms XRCC1andMGMT and risk of adult gliomas. Neuroepidemiology,2007,29;55–58.
73. J. Geng, Y.W. Zhang, G.C. Huang, L.B. Chen, XRCC1genetic polymorphismArg399Gln and gastric cancer risk: a meta-analysis. World J. Gastroenterol.2008,14;6733–6737.
74. D. Xing, J. Qi, X. Miao, W. Lu, W. Tan, D. Lin, Polymorphisms of DNA repair genesXRCC1and XPD and their associations with risk of esophageal squamous cellcarcinoma in a Chinese population. Int. J. Cancer2002,100;600–605.
75. R.C. Sobti, J. Singh, P. Kaur, S.S. Pachouri, E.A. Siddiqui, H.S. Bindra, XRCC1codon399and ERCC1codon751polymorphism, smoking, and drinking and risk of esophagealsquamous cell carcinoma in a North Indian population. CancerGenet. Cytogenet.2007,175;91–97.
1. Weber C A,Salazar E P,Stewart S A,et aI. ERCC2:cDNA cloning and molecularcharacterization of a human nucleotide excision repair gene with hgh homology to yeastRAD3. EMBO J,1990,9(5):1437。
2.蒋易,周李承,吴晓明,周宜开,雷于生,任恕.核苷酸切除修复基因XPD反义RNA表达载体的构建及功能研究[J].华中科技大学学报(医学版),2003,(03)。
3. Richard D W. Nucleotide excision repair in mammalian cells. J Biol Chem.1997Sep19;272(38):23465-8。
4. Lunn RM, Helzlsouer KJ, Parshad R, Umbach DM, Harris EL, Sanford KK, Bell DA.XPD polymorphisms: effects on DNA repair proficiency。 Carcinogenesis.2000Apr;21(4):551-5.
5. Shen MR, Jones IM, Mohrenweiser H. Nonconservative amino acid substitutionvariants exist at polymorphic frequency in DNA repair genes in healthy humans。CancerRes.1998Feb15;58(4):604-8.
6. Yang L,Parkin D M,Li L,et al. Time trends in cancer mortality in China:1987-1999.Int J Cancer,2003,106(5):771。
7. Misra R R, Ratnasinghe D, Tangrea J A, et al. Polymorphisms in the DNA repairgenes XPD,XRCCl,XRCC3,and APEIref-1. and the risk of lung cancer among malesmokers in Finland. Cancer Lett,2003,191(5):171。
8. Hou SM,Falt S,Angelini S,et al. The XPD variant alleles are associated with increasedaromatic DNA adduct level and lung cancer risk. Carcinogenesis,2002,23(5):599
9. Popanda O, Schattanberg T, Zaplana J, et al. Specific combinations of DNA repairgene variants and increased for non－small cell lung cancer.Carcinogen,2004,25(12):2433
10. Liang G,Xing D,Miao X,et al. Sequence variations in the DNA repair gene XPD andrisk of lung cancer in a Chincse population,Int J Cancer,2003,105(5):669
11. M Felicitas Lopez-Cima,Patricia GonzaleZ-Arriaga,Laura Garcia-Castro,et al.Polymorphisims in XPC,XPD,XRCC1,and XRCC3DNA repair genes and lungCancer risk in a population of Northem Spain.BMC Cancer,2007,10(7):162
12. Sturgis EM，Zheng R，Li I，et a1．XPD/ERCC2polymorphisms and risk of head andneck cancer：a ease．eontrol analysis．Carcinogenesis，2000，2l：2219—2223．
13. Goode EL，Ulrich CM，Potter JD，et a1．Polymorphisins in DNA repair genes andassociations with cancer risk．Cancer Epi—denfiol Biomarkers Prey，2002．11：1513一l530．
14. Dybdahl M，Frentz G，Vogel U，et a1．Low DNA repair is a risk factor in skincarcinogenesis：a study of basal cell carcinomain psoriasis patients．Mutat Res，1999，433：15-22。
15. Vogel U，Olsen A，Wallin H，et a1．Effectof polymorphisms in XPD，RAI，ASE-1and ERCC1on the risk of basal cell earci-noma among Caucasians after age50.CancerDetect Prev，2005，29：209-214．
16. Tomescu D．Kavanagh G。Ha T．et a1．Nu-cleotide excision repair gene XPDpoly-inorphisms and genetic predisposition to melanoma．Carcinogenesis，2001，22：403-408．
17. Baccarelli A，Calista D，Minghetti P，et a1．XPD gene polymorphism and hostcharac-teristics in the association with cutaneous malignant melanoma risk．Br JCancer，2004，90：497．502．
18. Yuan L, Cui D, Zhao EJ, Jia CZ, Wang LD, Lu WQ.XPD Lys751Gln polymorphism andesophageal cancer risk: a meta-analysis involving2288cases and4096controls. WorldJ Gastroenterol.2011May14;17(18):2343-8.
19. Yu HP，Wang XL，Sun X，el a1．Polymorphisms in the DNA repair gene XPI) andsusceptibility to esophageal squamous cell carcinoma．Cancer Genet Cytogenet，2004，154：10—15．
20. Ye W，Kumar R，Bacova G，et a1．The XPD751GIn allele is associated with anincreased risk for esophageal adenocarci—noma： a population—based case—controlstudy in Sweden．Carcinogenesis，2006，27：1835-1841．
21. Wang F，Chang D，Hu FL，et a1．DNA repair gene XPD polymorphisms and cancerrisk：a meta-analysis based on56case—control studies．Cancer Epidemiol BiomarkersPrey，2008，17：507-517．
22.张传臻,陈自平,徐昌青,宁涛,李丹萍,厚瑞萍. XPD基因与胃癌易感性的相关性[J].癌症,2009,(11)
23.娄毅，宋清斌，何向民，等．东北地区汉族人群DNA修复基因XPD单核苷酸多态性与胃癌的相关性．世界华人消化杂志，2006，14：3143-3146．
24. Huang WY， Chow WH， Rothman N， et al． Selected DNA repair polymorphismsand gastric cancer in Poland ［J］．Carcinogenesis，2005，26(8)：1354－1359．
25. Ye W， Kumar R， Bacova G， et al． The XPD751Gln allele is associated with anincreased risk for esophageal adenocarcinoma： a population-based case-control studyin Sweden ［J］． Carcinogenesis，2006，27(9)：1835－1841．
26. Ruzzo A，Canestrari E， Maltese P， et al． Polymorphisms in genes involved in DNArepair and metabolism of xenobiotics in individual susceptibility to sporadic diffusegastric cancer［J］． Clin Chem Lab Med，2007，45(7)：822－828．
27. McWilliams RR，Bamlet WR，Cunningham JM，et a1．Polymorphisms in DNA repairgenes，smoking，and pancreatic adenoearcinonm risk．Cancer Res，2008，68：4928－4935．
28. Li J， Manal MH， Melissa LB， et a1．The XPD Asp312Asn and Lys751GinPolymor—phisms，corresponding haplotype and pancreatic cancer risk．Cancer Lett，2007，245：61458．
29. Chen CC, Yang SY, Liu CJ等。Association of cytokine and DNA repair genepolymorphisms with hepatitis B-related hepatocellular carcinoma. Int J Epidemiol.2005Dec;34(6):1310-8. Epub2005Sep19.
30.曾小云，仇小强，纪龙，等．DNA修复基因XPD单核苷酸多态性和环境因素的交互作用与肝细胞癌的关联研究．中华流行病学杂志，2009，30：702-705．
31.许丽，吴一迁，金晏，等．DNA修复基因XPD多态性和肝细胞肝癌危险性的病例一对照研究．肿瘤，2004，24：526-529。
32. Long XD, Ma Y, Zhou YF, Yao JG, Ban FZ, Huang YZ, Huang BC. XPD codon312and751polymorphisms, and AFB1exposure, and hepatocellular carcinoma risk. BMCCancer.2009Nov17;9:400.
33. Zhang Y, Ding D, Wang X, Zhu Z, Huang M, He X. Lack of association between XPDLys751Gln and Asp312Asn polymorphisms and colorectal cancer risk: a meta-analysisof case-control studies. Int J Colorectal Dis.2011Oct;26(10):1257-64.
34. Stern MC, Johnson LR, Bell DA, Taylor JA. XPD codon751polymorphism,metabolism genes, smoking, and bladder cancer risk. Cancer Epidemiol BiomarkersPrev.2002Oct;11(10Pt1):1004-11.
35. Li C, Jiang Z, Liu X. XPD Lys(751)Gln and Asp (312)Asn polymorphisms and bladdercancer risk: a meta-analysis.
1. Rich AR, Lewis MR. The nature of allergy in tuberculosis as revealed by tissue culturestudies.Bull Johns Hopkins Hosp.1932;50:115–31.
2. George M, Vaughn JH. In vitro cell migration as a model for delayed hypersensitivity.Proc Soc Exp Biol Mes.1962;111:514–21.
3. David JR. Delayed hypersensitivity in vitro: its mediation by cell-free substancesformed by lymphoid cell-antigen interaction. Proceedings of the National Academy ofSciences of the United States of America.1966;56(1):72–7.
4. Bernhagen J, Calandra T, Mitchell RA, Martin SB, Tracey KJ, Voelter W, et al. MIF is apituitary derived cytokine that potentiates lethal endotoxaemia. Nature.1993;365(6448):756–9.
5. Bernhagen J, Krohn R, Lue H, Gregory JL, Zernecke A, Koenen RR, et al. MIF is anoncognate ligand of CXC chemokine receptors in inflammatory and atherogenic cellrecruitment. Nat Med.May;200713(5):587–96.
6. Calandra T, Roger T. Macrophage migration inhibitory factor: a regulator of innateimmunity.Nature Reviews Immunology.2003;3(10):791–800.
7. Simons D, Grieb G, Hristov M, Pallua N, Weber C, Bernhagen J, et al. Hypoxia-inducedendothelial secretion of macrophage migration inhibitory factor and role in endothelialprogenitor cell recruitment. J Cell Mol Med.2010Epub ahead of print.
8. Calandra T, Bernhagen J, Mitchell RA, Bucala R. The macrophage is an important andpreviously unrecognized source of macrophage migration inhibitory factor. Journal ofExperimental.Medicine.1994;179(6):1895–902.
9. Mitchell RA, Metz CN, Peng T, Bucala R. Sustained mitogen-activated protein kinase(MAPK) and cytoplasmic phospholipase A2activation by macrophage migrationinhibitory factor (MIF).Regulatory role in cell proliferation and glucocorticoid action.Journal of Biological Chemistry.1999;274(25):18100–6.
10. Mitchell RA, Liao H, Chesney J, Fingerle-Rowson G, Baugh J, David J, et al.Macrophage migration inhibitory factor (MIF) sustains macrophage proinflammatoryfunction by inhibiting p53: regulatory role in the innate immune response. Proceedingsof the National Academy of Sciences of the United States of America.2002;99(1):345–50.
11. Leng L, Metz CN, Fang Y, Xu J, Donnelly S, Baugh J, et al. MIF signal transductioninitiated by binding to CD74. Journal of Experimental Medicine.2003;197(11):1467–76.
12. Shi X, Leng L, Wang T, Wang W, Du X, Li J, et al. CD44is the signaling component ofthe macrophage migration inhibitory factor-CD74receptor complex. Immunity.2006;25(4):595–606.
13. Petrovsky N, Socha L, Silva D, Grossman AB, Metz C, Bucala R. Macrophagemigration inhibitory factor exhibits a pronounced circadian rhythm relevant to its roleas a glucocorticoid counter-regulator. Immunology&Cell Biology.2003;81(2):137–43.
14. Bacher M, Metz CN, Calandra T, Mayer K, Chesney J, Lohoff M, et al. An essentialregulatory role for macrophage migration inhibitory factor in T-cell activation.Proceedings of the National Academy of Sciences of the United States of America.1996;93(15):7849–54.
15. Rossi AG, Haslett C, Hirani N, Greening AP, Rahman I, Metz CN, et al. Humancirculating eosinophils secrete macrophage migration inhibitory factor (MIF). Potentialrole in asthma. Journal of Clinical Investigation.1998;101(12):2869–74.
16. Calandra T, Echtenacher B, Roy DL, Pugin J, Metz CN, Hultner L, et al. Protectionfrom septic shock by neutralization of macrophage migration inhibitory factor. NatureMedicine.2000;6(2):164–70.
17. Lehmann LE, Novender U, Schroeder S, Pietsch T, von Spiegel T, Putensen C, et al.Plasma levels of macrophage migration inhibitory factor are elevated in patients withsevere sepsis.Intensive Care Medicine.2001;27(8):1412–5.
18. de Mendonca-Filho HT, Gomes RV, de Almeida Campos LA, Tura B, Nunes EM,Gomes R, et al. Circulating levels of macrophage migration inhibitory factor areassociated with mild pulmonary dysfunction after cardiopulmonary bypass. Shock.2004;22(6):533–7.
19. Kofoed K, Andersen O, Kronborg G, Tvede M, Petersen J, Eugen-Olsen J, et al. Use ofplasma C-reactive protein, procalcitonin, neutrophils, macrophage migration inhibitoryfactor, soluble urokinase-type plasminogen activator receptor, and soluble triggeringreceptor expressed on myeloid cells-1in combination to diagnose infections: aprospective study. Critical Care (London, England).2007;11(2):R38.
20. Sprong T, Pickkers P, Geurts-Moespot A, van der Ven-Jongekrijg J, Neeleman C, KnaupM, et al. Macrophage migration inhibitory factor (MIF) in meningococcal septic shockand experimental human endotoxemia. Shock.2007;27(5):482–7.
21. Emonts M, Sweep FC, Grebenchtchikov N, Geurts-Moespot A, Knaup M, Chanson AL,et al.Association between high levels of blood macrophage migration inhibitory factor,inappropriate adrenal response, and early death in patients with severe sepsis. ClinicalInfectious Diseases.2007;44(10):1321–8.
22. Ostergaard C, Benfield T. Macrophage migration inhibitory factor in cerebrospinal fluidfrom patients with central nervous system infection. Critical Care (London, England).2009;13(3):R101.
23. Rahman SH, Menon KV, Holmfield JH, McMahon MJ, Guillou JP. Serum macrophagemigration inhibitory factor is an early marker of pancreatic necrosis in acutepancreatitis. Annals of Surgery.2007;245(2):282–9.
24. Otukesh H, Fereshtehnejad SM, Hoseini R, Hekmat S, Chalian H, Chalian M, et al.Urine macrophage migration inhibitory factor (MIF) in children with urinary tractinfection: a possible predictor of acute pyelonephritis. Pediatric Nephrology.2009;24(1):105–11.
25. Leech M, Metz C, Hall P, Hutchinson P, Gianis K, Smith M, et al. Macrophagemigration inhibitory factor in rheumatoid arthritis: evidence of proinflammatoryfunction and regulation by glucocorticoids. Arthritis&Rheumatism.1999;42(8):1601–8.
26. Kim HR, Park MK, Cho ML, Yoon CH, Lee SH, Park SH, et al. Macrophage migrationinhibitory factor upregulates angiogenic factors and correlates with clinical measures inrheumatoid arthritis. Journal of Rheumatology.2007;34(5):927–36.
27. Lan HY, Bacher M, Yang N, Mu W, Nikolic-Paterson DJ, Metz C, et al. The pathogenicrole of macrophage migration inhibitory factor in immunologically induced kidneydisease in the rat.Journal of Experimental Medicine.1997;185(8):1455–65.
28. Taniguchi Y, Yorioka N, Yamashita K, Masaki T, Yamakido M. Macrophage migrationinhibitory factor in IgA nephropathy. Kidney International.1998;54(6):2245–6.
29. Taniguchi Y, Yorioka N, Yamashita K, Masaki T, Yamakido M. Expression ofmacrophage migration inhibitory factor in patients with myeloperoxidaseanti-neutrophil cytoplasmic antibody-associated glomerulonephritis. ClinicalNephrology.2000;54(2):147–50.
30. Bruchfeld A, Carrero JJ, Qureshi AR, Lindholm B, Barany P, Heimburger O, et al.Elevated serum macrophage migration inhibitory factor (MIF) concentrations inchronic kidney disease (CKD) are associated with markers of oxidative stress andendothelial activation. Molecular Medicine.2009;15(3-4):70–5.
31. Foote A, Briganti EM, Kipen Y, Santos L, Leech M, Morand EF. Macrophage migrationinhibitory factor in systemic lupus erythematosus. Journal of Rheumatology.2004;31(2):268–73.
32. Wu SP, Leng L, Feng Z, Liu N, Zhao H, McDonald C, et al. Macrophage migrationinhibitory factor promoter polymorphisms and the clinical expression of scleroderma.Arthritis&Rheumatism.2006;54(11):3661–9.
33. Ohwatari R, Fukuda S, Iwabuchi K, Inuyama Y, Onoe K, Nishihira J. Serum level ofmacrophage migration inhibitory factor as a useful parameter of clinical course inpatients with Wegener’s granulomatosis and relapsing polychondritis. Annals ofOtology, Rhinology&Laryngology.2001;110(11):1035–40.
34. Calandra T, Bernhagen J, Metz CN, Spiegel LA, Bacher M, Donnelly T, et al. MIF as aglucocorticoid-induced modulator of cytokine production. Nature.1995;377(6544):68–71.
35. Fingerle-Rowson G, Koch P, Bikoff R, Lin X, Metz CN, Dhabhar FS, et al. Regulationof macrophage migration inhibitory factor expression by glucocorticoids in vivo.American Journal of Pathology.2003;162(1):47–56.
36. Flaster H, Bernhagen J, Calandra T, Bucala R. The macrophage migration inhibitoryfactorglucocorticoid dyad: regulation of inflammation and immunity. MolecularEndocrinology.2007;21(6):1267–80.
37. Otukesh H, Chalian M, Hoseini R, Chalian H, Hooman N, Bedayat A, et al. Urinemacrophage migration inhibitory factor in pediatric systemic lupus erythematosus.Clinical Rheumatology.2007;26(12):2105–7.
38. Yamaguchi E, Nishihira J, Shimizu T, Takahashi T, Kitashiro N, Hizawa N, et al.Macrophage migration inhibitory factor (MIF) in bronchial asthma. Clinical&Experimental Allergy.2000;30(9):1244–9.
39. Bargagli E, Olivieri C, Nikiforakis N, Cintorino M, Magi B, Perari MG, et al. Analysisof macrophage migration inhibitory factor (MIF) in patients with idiopathic pulmonaryfibrosis.Respiratory Physiology&Neurobiology.2009;167(3):261–7.
40. Kuper H, Adami HO, Trichopoulos D. Infections as a major preventable cause ofhuman cancer.Journal of Internal Medicine.2000;248(3):171–83.
41. Coussens LM, Werb Z. Inflammation and cancer. Nature.2002;420(6917):860–7.
42. Balkwill F, Mantovani A. Inflammation and cancer: back to Virchow? Lancet.2001;357(9255):539–45.
43. Bucala R, Donnelly SC. Macrophage migration inhibitory factor: a probable linkbetween inflammation and cancer. Immunity.2007;26(3):281–5.
44. Chesney J, Metz C, Bacher M, Peng T, Meinhardt A, Bucala R. An essential role formacrophage migration inhibitory factor (MIF) in angiogenesis and the growth of amurine lymphoma.Molecular Medicine.1999;5(3):181–91.
45. Shimizu T, Abe R, Nakamura H, Ohkawara A, Suzuki M, Nishihira J. High expressionof macrophage migration inhibitory factor in human melanoma cells and its role intumor cell growth and angiogenesis. Biochemical&Biophysical ResearchCommunications.1999;264(3):751–8.
46. Hudson JD, Shoaibi MA, Maestro R, Carnero A, Hannon GJ, Beach DH. Aproinflammatory cytokine inhibits p53tumor suppressor activity. Journal ofExperimental Medicine.1999;190(10):1375–82.
47. Repp AC, Mayhew ES, Apte S, Niederkorn JY: Human uveal melanoma cells producemacrophage migration-inhibitory factor to prevent lysis by NK cells. J Immunol2000;165:710–715.
48. Abe R, Peng T, Sailors J, Bucala R, Metz CN:Regulation of the CTL response bymacrophage migration inhibitory factor. J Immunol2001;166:747–753.
49. Meyer-Siegler KL, Bellino MA, Tannenbaum M: Macrophage migration inhibitoryfactor evaluation compared with prostate specific antigen as a biomarker in patientswith prostate carcinoma. Cancer2002;94:1449–1456.
50. Hira E, Ono T, Dhar DK, El-Assal ON, Hishikawa Y, Yamanoi A, Nagasue N:Overexpression of macrophage migration inhibitory factor induces angiogenesis anddeteriorates prognosis after radical resection for hepatocellular carcinoma. Cancer2005;103:588–598.
51. Legendre H, Decaestecker C, Nagy N, Hendlisz A, Schuring MP, Salmon I, GabiusHJ,Pector JC, Kiss R: Prognostic values of galectin-3and the macrophage migrationinhibitory factor (MIF) in human colorectal cancers.Mod Pathol2003;16:491–504.
52. Rogge L: A genomic view of helper T cell subsets.Ann NY Acad Sci2002;975:57–67.
53. Mitchell RA, Liao H, Chesney J, Fingerle-Rowson G, Baugh J, David J, Bucala R:Macrophage migration inhibitory factor (MIF) sustains macrophage proinflammatoryfunction by inhibiting p53: regulatory role in the innate immune response. Proc NatlAcad Sci USA2002;99:345–350.
54. Mitchell RA: Mechanisms and effectors of MIF-dependent promotion oftumourigenesis.Cell Signal2004;16:13–19.
55. Onodera S, Suzuki K, Matsuno T, Kaneda K,Takagi M, Nishihira J: Macrophagemigration inhibitory factor induces phagocytosis of foreign particles by macrophages inautocrine and paracrine fashion. Immunology1997;92:131–137.
56. Takahashi N, Nishihira J, Sato Y, Kondo M,Ogawa H, Ohshima T, Une Y, Todo S:Involvement of macrophage migration inhibitory factor (MIF) in the mechanism oftumor cell growth. Mol Med1998;4:707–714.
57. Meyer-Siegler KL, Iczkowski KA, Leng L,Bucala R, Vera PL: Inhibition ofmacrophage migration inhibitory factor or its receptor (CD74) attenuates growth andinvasion of DU-145prostate cancer cells. J Immunol2006;177:8730–8739.
58. Rendon BE, Roger T, Teneng I, Zhao M, Al-Abed Y, Calandra T, Mitchell RA:Regulation of human lung adenocarcinoma cell migration and invasion by macrophagemigration inhibitory factor. J Biol Chem2007;282:29910–29918.
59. Amin MA, Volpert OV, Woods JM, Kumar P,Harlow LA, Koch AE: Migrationinhibitory factor mediates angiogenesis via mitogenactivated protein kinase andphosphatidylinositol kinase. Circ Res2003;93:321–329.
60. Bacher M, Schrader J, Thompson N, Kuschela K, Gemsa D, Waeber G, Schlegel J:Up-regulation of macrophage migration inhibitory factor gene and protein expressionin glial tumor cells during hypoxic and hypoglycemic stress indicates a critical role forangiogenesis in glioblastoma multiforme. Am J Pathol2003;162:11–17.
61. Baugh JA, Gantier M, Li L, Byrne A, Buckley A, Donnelly SC: Dual regulation ofmacrophage migration inhibitory factor (MIF) expression in hypoxia by CREB andHIF-1. Biochem Biophys Res Commun2006;347:895–903.
62. Welford SM, Bedogni B, Gradin K, Poellinger L, Broome Powell M, Giaccia AJ:HIF1-α delays premature senescence throughthe activation of MIF. Genes Dev2006;20:3366–3371.
63. Winner M, Koong AC, Rendon BE, Zundel W, Mitchell RA: Amplification of tumorhypoxic responses by macrophage migration inhibitory factor-dependenthypoxia-inducible factor stabilization. Cancer Res2007;67:186–193.
64. Fingerle-Rowson G, Petrenko O, Metz CN,Forsthuber TG, Mitchell R, Huss R, MollU,Muller W, Bucala R: The p53-dependent effects of macrophage migration inhibitoryfactor revealed by gene targeting. Proc Natl Acad Sci USA2003;100:9354–9359.
65. Petrenko O, Fingerle-Rowson G, Peng T,Mitchell RA, Metz CN: Macrophage migrationinhibitory factor deficiency is associated with altered cell growth and reducedsusceptibility to ras-mediated transformation. J Biol Chem2003;278:11078–11085.
66. Nemajerova A, Mena P, Fingerle-Rowson G,Moll UM, Petrenko O: Impaired DNAdamage checkpoint response in MIF-deficient mice. EMBO J2007.
67. Winner M, Leng L, Zundel W, Mitchell RA:Macrophage migration inhibitory factormanipulation and evaluation in tumoral hypoxic adaptation. Methods Enzymol2007;435:355–369.
68. Altinoz MA, Korkmaz R: NF-κB, macrophage migration inhibitory factor andcyclooxygenase-inhibitions as likely mechanisms behind the acetaminophen-andNSAID-prevention of the ovarian cancer. Neoplasma2004;51:239–247.
69. Mor G, Visintin I, Lai Y, Zhao H, Schwartz P, Rutherford T, et al. Serum proteinmarkers for early detection of ovarian cancer. Proceedings of the National Academy ofSciences of the United States of America.2005;102(21):7677–82.
70. Kim K, Visintin I, Alvero AB, Mor G. Development and validation of a protein-basedsignature for the detection of ovarian cancer. Clinics in Laboratory Medicine.2009;29(1):47–55.
71. Ren Y, Law S, Huang X, Lee PY, Bacher M, Srivastava G, et al. Macrophage migrationinhibitory factor stimulates angiogenic factor expression and correlates withdifferentiation and lymph node status in patients with esophageal squamous cellcarcinoma. Annals of Surgery.2005;242(1):55–63.
72. Shun CT, Lin JT, Huang SP, Lin MT, Wu MS. Expression of macrophage migrationinhibitory factor is associated with enhanced angiogenesis and advanced stage ingastric carcinomas. World Journal of Gastroenterology.2005;11(24):3767–71.
73. Camlica H, Duranyildiz D, Oguz H, Oral EN, Yasasever V. The diagnostic value ofmacrophage migration inhibitory factor (MIF) in gastric cancer. Pathology OncologyResearch.2008;14(1):79–83.
74. Mohri Y, Mohri T, Wei W, Qi YJ, Martin A, Miki C, et al. Identification of macrophagemigration inhibitory factor and human neutrophil peptides1-3as potential biomarkersfor gastric cancer. British Journal of Cancer.2009;101(2):295–302.
75. Yasasever V, Camlica H, Duranyildiz D, Oguz H, Tas F, Dalay N. Macrophagemigration inhibitory factor in cancer. Cancer Investigation.2007;25(8):715–9.
76. Baugh JA, Chitnis S, Donnelly SC, Monteiro J, Lin X, Plant BJ, et al. A functionalpromoter polymorphism in the macrophage migration inhibitory factor (MIF) geneassociated with disease severity in rheumatoid arthritis. Genes&Immunity.2002;3(3):170–6.
77. Radstake TR, Sweep FC, Welsing P, Franke B, Vermeulen SH, Geurts-Moespot A, et al.Correlation of rheumatoid arthritis severity with the genetic functional variants andcirculating levels of macrophage migration inhibitory factor. Arthritis&Rheumatism.2005;52(10):3020–9.
78. Meyer-Siegler KL, Vera PL, Iczkowski KA, Bifulco C, Lee A, Gregersen PK, et al.Macrophage migration inhibitory factor (MIF) gene polymorphisms are associated withincreased prostate cancer incidence. Genes&Immunity.2007;8(8):646–52.
79. Arisawa T, Tahara T, Shibata T, Nagasaka M, Nakamura M, Kamiya Y, et al. Functionalpromoter polymorphisms of the macrophage migration inhibitory factor gene in gastriccarcinogenesis. Oncology Reports.2008;19(1):223–8.
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