环境因素及COMT基因多态性与乳腺癌关系的病例对照研究
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摘要
目的:本研究通过1:1配对的病例对照研究方法,分析外源性环境因素暴露、COMT基因多态性与乳腺癌的关系,为乳腺癌的病因学研究及防治提供科学依据.方法:采用以医院为基础1:1配比的病例对照研究.自2010年10月～2011年10月止,收集唐山市各大医院就诊的120例新发且经病理学确诊的女性乳腺癌患者,同时选取与病例同期住院非肿瘤、非生殖内分泌系统疾病的120例女性患者为对照,年龄相差在5岁以内,根据统一的调查表进行流行病学调查,并采集患者外周静脉血,用盐析法提取研究对象全血中DNA,采用聚合酶链反应-限制性片段多态性(PCR-RFLP)方法检测各研究对象的COMT基因多态性,所有资料用Excel建库,数据分析采用SPSS16.0软件,计算相对危险度(OR)及其95%可信区间(CI).结果:居住地环境污染(OR=13.17,95%CI:2.73~63.56),被动吸烟≥10年(OR=17.80,95%CI:4.04~78.47),农药使用≥10年(OR=5.66,95%CI:1.24~25.94)为乳腺癌危险因素.地震后一年内很少闻到农药气味(OR=0.10,95%CI:0.03~0.35),烹调时使用排油烟设备(OR=0.16,95%CI:0.03~0.88)为保护因素;病例与对照基因型频率分布差异有统计学意义(χ2=8.28,P<0.05),基因型位点至少携带一个突变等位基因(杂合型GA和突变纯合型AA)的为易感基因型,野生纯合型GG为参照基因型,结果提示病例与对照野生型杂合子基因型分布和突变型纯合子分布频率差异均有统计学意义(OR=1.79,95%CI:0.57~5.56;OR=1.15,95%CI:0.35~3.85),即携带杂合型和突变纯合型者患乳腺癌的风险分别为野生纯合型的1.79和1.15倍.结论:居住地环境污染、被动吸烟≥10年、农药使用≥10年为乳腺癌危险因素.地震后接触有机氯农药少,烹调时使用排油设备为保护因素;携带COMTAA突变基因型的患者患乳腺癌的风险性增高.
In present study,a hospital-based 1:1 matched case-control study was conducted to explore the role of COMT gene polymorphism and to provide theory foundation for studying the etiology and primary prevention of breast cancer.Methods: 1:1 matched case-control study method was adopted.All cases and controls were recruited from hospitals in Tangshan.120 newly diagnosed female breast cancer patients from October 2010 to October 2011 were selected as cases,which were pathologically confirmed.Controls were identified as patients at the same hospital,with the exception of gynecological,endocrinological and oncological diseases.Between the cases and controls,the difference of age was not over five years.All subjects were investigated by face to face interview according to the same questionnaire.DNA of subjects was extracted by salting out method,and detected COMT genotype by polymerase chain reaction-restriction fragment polymorphism(PCR-RFLP).The database was set up by excel and analyzed using the statistical software SPSS16.0 version.Results: 1 The environmental risk factors of breast cancer were environmental pollution of residence(OR=13.17,95%CI:2.73~63.56),passive smoking exceeding 10 years(OR=17.80,95%CI:4.07~78.47),and pesticide using exceeding 10 years(OR=5.66,95%CI:1.24~25.94).After the earthquake within one year the pesticide odor was smell little(OR=0.10,95%CI:0.03~0.35)and equipment using in cooking(OR=0.16,95%CI: 0.03~0.88)were all protective factors.2 The differences of the frequencies of COMT were statistically significant(χ2=8.28,P<0.05).The genotype of GA and AA were susceptible genotype.Refer to GG,the OR value of breast cancer for ones carrying GA and AA were 1.79(95%CI:0.57~5.56;) and 1.15(95%CI: 0.35~3.85).Conclusions: 1 The environmental risk factors of breast cancer are environmental pollution of residence,passive smoking exceeding 10 years and pesticide using exceeding 10 years.Few exposure to pesticide after the earthquake and equipment using in cooking were protective factors.2 Women with COMT AA variant genotype may have more risks of breast cancer.
In present study,a hospital-based 1:1 matched case-control study was conducted to explore the role of COMT gene polymorphism and to provide theory foundation for studying the etiology and primary prevention of breast cancer.Methods: 1:1 matched case-control study method was adopted.All cases and controls were recruited from hospitals in Tangshan.120 newly diagnosed female breast cancer patients from October 2010 to October 2011 were selected as cases,which were pathologically confirmed.Controls were identified as patients at the same hospital,with the exception of gynecological,endocrinological and oncological diseases.Between the cases and controls,the difference of age was not over five years.All subjects were investigated by face to face interview according to the same questionnaire.DNA of subjects was extracted by salting out method,and detected COMT genotype by polymerase chain reaction-restriction fragment polymorphism(PCR-RFLP).The database was set up by excel and analyzed using the statistical software SPSS16.0 version.Results: 1 The environmental risk factors of breast cancer were environmental pollution of residence(OR=13.17,95%CI:2.73~63.56),passive smoking exceeding 10 years(OR=17.80,95%CI:4.07~78.47),and pesticide using exceeding 10 years(OR=5.66,95%CI:1.24~25.94).After the earthquake within one year the pesticide odor was smell little(OR=0.10,95%CI:0.03~0.35)and equipment using in cooking(OR=0.16,95%CI: 0.03~0.88)were all protective factors.2 The differences of the frequencies of COMT were statistically significant(χ2=8.28,P<0.05).The genotype of GA and AA were susceptible genotype.Refer to GG,the OR value of breast cancer for ones carrying GA and AA were 1.79(95%CI:0.57~5.56;) and 1.15(95%CI: 0.35~3.85).Conclusions: 1 The environmental risk factors of breast cancer are environmental pollution of residence,passive smoking exceeding 10 years and pesticide using exceeding 10 years.Few exposure to pesticide after the earthquake and equipment using in cooking were protective factors.2 Women with COMT AA variant genotype may have more risks of breast cancer.
引文
[1]邹其嘉,王子平,陈非比,等.唐山地震灾区社会恢复与社会问题研究[M].北京:地震出版社,1997:398-401.
[2]RUSSO J,RUSSO IH.The role of estrogen in the initiation of breast cancer[J].J Steroid Biochem Mol Biol,2006,102(15):892-961.
[3]SHEILA D,NADY R,ROY MOND L,et al.Catechol-O-methyl-transferase(COMT)-mediated metabolism of catechol estrogens:comparison of wild-typeand variant COMT Isoforms[J].Cancer Research,2001(61):6716-6722.
[4]裴广军,付莉,崔亚玲,等.中国女性乳腺癌危险因素的Meta分析[J].中国妇幼保健,2008,23(4):2650-2652.
[5]王启俊,李玲,祝伟星,等.北京市乳腺癌危险因素病例对照研究[J].中国慢性病预防与控制,2000,8(4):165-167.
[6]方亚,胡海兰.女性乳腺癌危险因素及其变化[J].中国卫生统计,2009,26(3):241-243.
[7]林红,施莹莹,黄玲,等.珠海市农村地区妇女乳腺癌危险因素分析[J].岭南现代临床外科,2008,8(1):28-29.
[8]LI CI,MALONE KE,DALING JR.The relationship between various measures of cigarette smoking and risk of breast cancer among older women 65-79years of age(United States)[J].Cancer Causes Control,2005,16(8):975.
[9]MATSUL A,IKEDA T,ENOMATO K,et al.Progression of human breast cancers to the metdtatic state is linked to genotypes of catechol-O-methyltransferase[J].Cancer Lett,2009,150(1):23-31.
[10]谭文,齐军,邢德印,等.雌激素代谢基因COMT和CYP17单核苷酸多态与女性乳腺癌风险的关系[J].中华肿瘤杂志,2003,25(5):453-456.
[11]陈娜,武彪.乳腺癌易感基因的研究进展[J].江西医药,2010,45(5):496-499.
[2]RUSSO J,RUSSO IH.The role of estrogen in the initiation of breast cancer[J].J Steroid Biochem Mol Biol,2006,102(15):892-961.
[3]SHEILA D,NADY R,ROY MOND L,et al.Catechol-O-methyl-transferase(COMT)-mediated metabolism of catechol estrogens:comparison of wild-typeand variant COMT Isoforms[J].Cancer Research,2001(61):6716-6722.
[4]裴广军,付莉,崔亚玲,等.中国女性乳腺癌危险因素的Meta分析[J].中国妇幼保健,2008,23(4):2650-2652.
[5]王启俊,李玲,祝伟星,等.北京市乳腺癌危险因素病例对照研究[J].中国慢性病预防与控制,2000,8(4):165-167.
[6]方亚,胡海兰.女性乳腺癌危险因素及其变化[J].中国卫生统计,2009,26(3):241-243.
[7]林红,施莹莹,黄玲,等.珠海市农村地区妇女乳腺癌危险因素分析[J].岭南现代临床外科,2008,8(1):28-29.
[8]LI CI,MALONE KE,DALING JR.The relationship between various measures of cigarette smoking and risk of breast cancer among older women 65-79years of age(United States)[J].Cancer Causes Control,2005,16(8):975.
[9]MATSUL A,IKEDA T,ENOMATO K,et al.Progression of human breast cancers to the metdtatic state is linked to genotypes of catechol-O-methyltransferase[J].Cancer Lett,2009,150(1):23-31.
[10]谭文,齐军,邢德印,等.雌激素代谢基因COMT和CYP17单核苷酸多态与女性乳腺癌风险的关系[J].中华肿瘤杂志,2003,25(5):453-456.
[11]陈娜,武彪.乳腺癌易感基因的研究进展[J].江西医药,2010,45(5):496-499.
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