妇科恶性肿瘤与微生物菌群的关系
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摘要
近年来,随着人口老龄化和生活方式的不断改变,妇科恶性肿瘤的发病呈现上升趋势,严重损害女性生命健康。目前关于妇科恶性肿瘤的病因、发病机制尚未完全阐明。除遗传因素外,环境因素在肿瘤的发生、发展中也扮演着重要的角色。女性生殖道的解剖特点使其处于开放性结构,易受各种病原体的入侵。高通量测序及序列识别技术的不断发展与成熟,使得微生物菌群与妇科恶性肿瘤的关系成为研究的热点,阐明微生物菌群对妇科恶性肿瘤的影响至关重要,本文对微生物菌群与妇科恶性肿瘤关系的研究进展作一综述,为妇科恶性肿瘤的防治提供科学依据。
In recent years,with the aging of the population and lifestyle changes,the incidence of gynecological malignancies is on the rise,which has seriously damaged women′s life and health.At present,the etiology and pathogenesis of gynecological malignancies have not been fully elucidated.In addition to genetic factors,environmental factors play an important role in the occurrence and development of tumors.The anatomical features of female reproductive tract show that it is an open structure that is vulnerable to invasion by various pathogens.With the continuous development and maturation of high-throughput sequencing and sequence identification technologies,the relationship between microbial flora and gynecological malignancies has become a hotspot in the field of research.Elucidating the effect of microflora on gynecologic malignancies is of utmost importance.This article reviews the progress in research on the relation between microbial flora and gynecological malignancies,in order to provide scientific evidences for the prevention and treatment of gynecological malignancies.
In recent years,with the aging of the population and lifestyle changes,the incidence of gynecological malignancies is on the rise,which has seriously damaged women′s life and health.At present,the etiology and pathogenesis of gynecological malignancies have not been fully elucidated.In addition to genetic factors,environmental factors play an important role in the occurrence and development of tumors.The anatomical features of female reproductive tract show that it is an open structure that is vulnerable to invasion by various pathogens.With the continuous development and maturation of high-throughput sequencing and sequence identification technologies,the relationship between microbial flora and gynecological malignancies has become a hotspot in the field of research.Elucidating the effect of microflora on gynecologic malignancies is of utmost importance.This article reviews the progress in research on the relation between microbial flora and gynecological malignancies,in order to provide scientific evidences for the prevention and treatment of gynecological malignancies.
引文
[1]CHEN Wanqing,ZHENG Rongshou,ZHANG Siwei,et al.Report of cancer incidence and mortality in China,2013[J].China Cancer,2017,26(1):1-7.(in Chinese)陈万青,郑荣寿,张思维,等.2013年中国恶性肿瘤发病和死亡分析[J].中国肿瘤,2017,26(1):1-7.
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[4]Champer M,Wong AM,Champer J,et al.The role of the vaginal microbiome in gynecological cancer[J].BJOG,2017,125(3):309-315.
[5]Spiegel,Carol A.Bacterial vaginosis[J].Rev Med Microbiol,2002,13(2):43-51.
[6]Green KA,Zarek SM,Catherino WH.Gynecologic health and disease in relation to the microbiome of the female reproductive tract[J].Fertil Steril,2015,104(6):1351-1357.
[7]Gao W,Weng J,Gao Y,et al.Comparison of the vaginal microbiota diversity of women with and without human papillomavirus infection:A cross-sectional study[J].BMC Infect Dis,2013,13:271-281.
[8]Mitra A,Macintyre DA,Lee YS,et al.Cervical intraepithelial neoplasia disease progression is associated with increased vaginal microbiome diversity[J].Sci Rep,2015,5:16865.
[9]Kyrgiou M,Mitra A,Moscicki AB.Does the vaginal microbiota play a role in the development of cervical cancer?[J].Transl Res,2017,179:168-182.
[10]Walther-António MR,Chen J,Multinu F,et al.Potential contribution of the uterine microbiome in the development of endometrial cancer[J].Genome Med,2016,8(1):122-137.
[11]Furumoto H,Irahara M.Human papilloma virus(HPV)and cervical cancer[J].J Med Invest,2002,49(3/4):124-133.
[12]Zhang PP,Zhou L,Cao JS,et al.Possible epithelial ovarian cancer association with HPV18or HPV33infection[J].Asian Pac J Cancer Prev,2016,17(6):2959-2964.
[13]Lee JE,Lee S,Lee H,et al.Association of the vaginal microbiota with human papillomavirus infection in a Korean twin cohort[J].PLoS One,2013,8(5):e63514.
[14]Mubangizi L,Namusoke F,Mutyaba T.Aerobic cervical bacteriology and antibiotic sensitivity patterns in patients with advanced cervical cancer before and after radiotherapy at a national referral hospital in Uganda[J].Int J Gynaecol Obstet,2014,126(1):37-40.
[15]Kosikowska U,Biernasiuk A,Rybojad P,et al.Haemophilus parainfluenzae as a marker of the upper respiratory tract microbiota changes under the influence of preoperative prophylaxis with or without postoperative treatment in patients with lung cancer[J].BMC Microbiol,2016,16:62.
[16]Huse SM,Ye Y,Zhou Y,et al.A core human microbiome as viewed through 16SrRNA sequence clusters[J].PLoS One,2012,7(6):e34242.
[17]Jumpstart consortium human microbiome project data generation working group.Evaluation of 16SrDNA-based community profiling for human microbiome research[J].PLoS One,2012,7(6):e39315.
[18]Scholz CF,Poulsen K,Kilian M.Novel molecular method for identification of Streptococcus pneumoniae applicable to clinical microbiology and 16SrRNA sequence-based microbiome studies[J].J Clin Microbiol,2012,50(6):1968-1973.
[19]Chakravorty S,Helb D,Burday M,et al.A detailed analysis of 16Sribosomal RNA gene segments for the diagnosis of pathogenic bacteria[J].J Microbiol Meth,2007,69(2):330-339.
[20]Piyathilake CJ,Ollberding NJ,Kumar R,et al.Cervical microbiota associated with higher grade cervical intraepithelial neoplasia in women infected with high-risk human papillomaviruses[J].Cancer Prev Res,2016,9(5):357-366.
[21]Seo SS,Oh H,Lee JK,et al.Combined effect of diet and cervical microbiome on the risk of cervical intraepithelial neoplasia[J].Clin Nutr,2016,35(6):1434-1441.
[22]Oh HY,Kim BS,Seo SS,et al.The association of uterine cervical microbiota with an increased risk for cervical intraepithelial neoplasia in Korea[J].Clin Microbiol Infect,2015,21(7):674.
[23]Audirac-Chalifour A,Torres-Poveda K,Bahena-Román M,et al.Cervical microbiome and cytokine profile at various stages of cervical cancer:A pilot study[J].PLoS One,2016,11(4):e0153274.
[24]Wang WL,Xu SY,Ren ZG,et al.Application of metagenomics in the human gut microbiome[J].World J Gastroentero,2015,21(3):803-814.
[25]Qin J,Li R,Raes J,et al.A human gut microbial gene catalogue established by metagenomic sequencing[J].Nature,2010,464(7285):59-65.
[26]Xu P,Gunsolley J.Application of metagenomics in understanding oral health and disease[J].Virulence,2014,5(3):424-432.
[27]Raes J,Korbel JO,Lercher MJ,et al.Prediction of effective genome size in metagenomic samples[J].Genome Biol,2007,8(1):R10.
[28]Jemal A,Bray F,Center MM,et al.Global cancer statistics[J].CA Cancer J Clin,2011,61(2):69-90.
[29]Mu1oz N.Human papillomavirus and cancer:The epidemiological evidence[J].J Clin Virol,2000,19(1/2):1-5.
[30]Di Paola M,Sani C,Clemente A M,et al.Characterization of cervico-vaginal microbiota in women developing persistent highrisk Human Papillomavirus infection[J].Sci Rep,2017,7(1):10200.
[31]XIE Xing,GOU Wenli.Obstetrics and Gynecology[M].8th ed.Beijing:People Health Publishing House,2013:313-316.(in Chinese)谢幸,苟文丽.妇产科学[M].8版.北京:人民卫生出版社,2013:313-316.
[32]Nagle CM,Olsen CM,Ibiebele TI,et al.Glycemic index,glycemic load and endometrial cancer risk:Results from the Australian National Endometrial Cancer study and an updated systematic review and meta-analysis[J].Eur J Nutr,2013,52(2):705-715.
[33]Calle EE,Kaaks R.Overweight,obesity and cancer:Epidemiological evidence and proposed mechanisms[J].Nature Reviews Cancer,2004,4(8):579-591.
[34]Choi J,Joseph L,Pilote L.Obesity and C-reactive protein in various populations:A systematic review and meta-analysis[J].Obes Rev,2013,14(3):232-244.
[35]Oh HY,Seo SS,Kong JS,et al.Association between obesity and cervical microflora dominated by Lactobacillus iners in Korean women[J].J Clin Microbiol,2015,53(10):3304-3309.
[36]Dossus L,Lukanova A,Rinaldi S,et al.Hormonal,metabolic,and inflammatory profiles and endometrial cancer risk within the EPIC cohort-A factor analysis[J].Am J Epidemiol,2013,177(8):787-99.
[37]Yang TK,Chung CJ,Chung SD,et al.Risk of endometrial cancer in women with pelvic inflammatory disease:A nationwide population-based retrospective cohort study[J].Medicine(Baltimore),2015,94(34):e1278..
[38]Hunn J,Rodriguez GC.Ovarian cancer:Etiology,risk factors,and epidemiology[J].Clin Obstet Gynecol,2012,55(1):3-23.
[39]Rosa MI,Silva GD,de Azedo Sim7es PW,et al.The prevalence of human papillomavirus in ovarian cancer:A systematic review[J].Int J Gynecol Cancer,2013,23(3):437-441.
[40]Shanmughapriya S,Senthilkumar G,Vinodhini K,et al.Viral and bacterial aetiologies of epithelial ovarian cancer[J].Eur JClin Microbiol Infect Dis,2012,31(9):2311-2317.
[41]Ingerslev K,Hogdall E,Schnack TH,et al.The potential role of infectious agents and pelvic inflammatory disease in ovarian carcinogenesis[J].Infect Agents Cancer,2017,12:25.
[42]Francescone R,Hou V,Grivennikov SI.Microbiome,inflammation,and cancer[J].Cancer J,2014,20(3):181-189.
[43]Shan W,Liu J.Inflammation:A hidden path to breaking the spell of ovarian cancer[J].Cell Cycle,2009,8(19):3107-3111.
[44]Risch HA,Howe GR.Pelvic inflammatory disease and the risk of epithelial ovarian cancer[J].Cancer Epidemiol Biomarkers Prev,1995,4(5):447-551.
[45]Lin HW,Tu YY,Lin SY,et al.Risk of ovarian cancer in women with pelvic inflammatory disease:A population-based study[J].Lancet Oncol,2011,12(9):900-904.
[46]Schwabe RF,Jobin C.The microbiome and cancer[J].Nat Rev Cancer,2013,13(11):800-812.
[47]Bultman SJ.Emerging roles of the microbiome in cancer[J].Carcinogenesis,2014,35(2):249-255.
[2]Hooper LV,Bry L,Falk PG,et al.Host-microbial symbiosis in the mammalian intestine:Exploring an internal ecosystem[J].Bioessays,1998,20(4):336-343.
[3]Haldar S,Kapil A,Sood S,et al.Female reproductive tract microbiome in gynecological health and problems[J].J Reprod Health Med,2016,2(Suppl 2):S48-S54.
[4]Champer M,Wong AM,Champer J,et al.The role of the vaginal microbiome in gynecological cancer[J].BJOG,2017,125(3):309-315.
[5]Spiegel,Carol A.Bacterial vaginosis[J].Rev Med Microbiol,2002,13(2):43-51.
[6]Green KA,Zarek SM,Catherino WH.Gynecologic health and disease in relation to the microbiome of the female reproductive tract[J].Fertil Steril,2015,104(6):1351-1357.
[7]Gao W,Weng J,Gao Y,et al.Comparison of the vaginal microbiota diversity of women with and without human papillomavirus infection:A cross-sectional study[J].BMC Infect Dis,2013,13:271-281.
[8]Mitra A,Macintyre DA,Lee YS,et al.Cervical intraepithelial neoplasia disease progression is associated with increased vaginal microbiome diversity[J].Sci Rep,2015,5:16865.
[9]Kyrgiou M,Mitra A,Moscicki AB.Does the vaginal microbiota play a role in the development of cervical cancer?[J].Transl Res,2017,179:168-182.
[10]Walther-António MR,Chen J,Multinu F,et al.Potential contribution of the uterine microbiome in the development of endometrial cancer[J].Genome Med,2016,8(1):122-137.
[11]Furumoto H,Irahara M.Human papilloma virus(HPV)and cervical cancer[J].J Med Invest,2002,49(3/4):124-133.
[12]Zhang PP,Zhou L,Cao JS,et al.Possible epithelial ovarian cancer association with HPV18or HPV33infection[J].Asian Pac J Cancer Prev,2016,17(6):2959-2964.
[13]Lee JE,Lee S,Lee H,et al.Association of the vaginal microbiota with human papillomavirus infection in a Korean twin cohort[J].PLoS One,2013,8(5):e63514.
[14]Mubangizi L,Namusoke F,Mutyaba T.Aerobic cervical bacteriology and antibiotic sensitivity patterns in patients with advanced cervical cancer before and after radiotherapy at a national referral hospital in Uganda[J].Int J Gynaecol Obstet,2014,126(1):37-40.
[15]Kosikowska U,Biernasiuk A,Rybojad P,et al.Haemophilus parainfluenzae as a marker of the upper respiratory tract microbiota changes under the influence of preoperative prophylaxis with or without postoperative treatment in patients with lung cancer[J].BMC Microbiol,2016,16:62.
[16]Huse SM,Ye Y,Zhou Y,et al.A core human microbiome as viewed through 16SrRNA sequence clusters[J].PLoS One,2012,7(6):e34242.
[17]Jumpstart consortium human microbiome project data generation working group.Evaluation of 16SrDNA-based community profiling for human microbiome research[J].PLoS One,2012,7(6):e39315.
[18]Scholz CF,Poulsen K,Kilian M.Novel molecular method for identification of Streptococcus pneumoniae applicable to clinical microbiology and 16SrRNA sequence-based microbiome studies[J].J Clin Microbiol,2012,50(6):1968-1973.
[19]Chakravorty S,Helb D,Burday M,et al.A detailed analysis of 16Sribosomal RNA gene segments for the diagnosis of pathogenic bacteria[J].J Microbiol Meth,2007,69(2):330-339.
[20]Piyathilake CJ,Ollberding NJ,Kumar R,et al.Cervical microbiota associated with higher grade cervical intraepithelial neoplasia in women infected with high-risk human papillomaviruses[J].Cancer Prev Res,2016,9(5):357-366.
[21]Seo SS,Oh H,Lee JK,et al.Combined effect of diet and cervical microbiome on the risk of cervical intraepithelial neoplasia[J].Clin Nutr,2016,35(6):1434-1441.
[22]Oh HY,Kim BS,Seo SS,et al.The association of uterine cervical microbiota with an increased risk for cervical intraepithelial neoplasia in Korea[J].Clin Microbiol Infect,2015,21(7):674.
[23]Audirac-Chalifour A,Torres-Poveda K,Bahena-Román M,et al.Cervical microbiome and cytokine profile at various stages of cervical cancer:A pilot study[J].PLoS One,2016,11(4):e0153274.
[24]Wang WL,Xu SY,Ren ZG,et al.Application of metagenomics in the human gut microbiome[J].World J Gastroentero,2015,21(3):803-814.
[25]Qin J,Li R,Raes J,et al.A human gut microbial gene catalogue established by metagenomic sequencing[J].Nature,2010,464(7285):59-65.
[26]Xu P,Gunsolley J.Application of metagenomics in understanding oral health and disease[J].Virulence,2014,5(3):424-432.
[27]Raes J,Korbel JO,Lercher MJ,et al.Prediction of effective genome size in metagenomic samples[J].Genome Biol,2007,8(1):R10.
[28]Jemal A,Bray F,Center MM,et al.Global cancer statistics[J].CA Cancer J Clin,2011,61(2):69-90.
[29]Mu1oz N.Human papillomavirus and cancer:The epidemiological evidence[J].J Clin Virol,2000,19(1/2):1-5.
[30]Di Paola M,Sani C,Clemente A M,et al.Characterization of cervico-vaginal microbiota in women developing persistent highrisk Human Papillomavirus infection[J].Sci Rep,2017,7(1):10200.
[31]XIE Xing,GOU Wenli.Obstetrics and Gynecology[M].8th ed.Beijing:People Health Publishing House,2013:313-316.(in Chinese)谢幸,苟文丽.妇产科学[M].8版.北京:人民卫生出版社,2013:313-316.
[32]Nagle CM,Olsen CM,Ibiebele TI,et al.Glycemic index,glycemic load and endometrial cancer risk:Results from the Australian National Endometrial Cancer study and an updated systematic review and meta-analysis[J].Eur J Nutr,2013,52(2):705-715.
[33]Calle EE,Kaaks R.Overweight,obesity and cancer:Epidemiological evidence and proposed mechanisms[J].Nature Reviews Cancer,2004,4(8):579-591.
[34]Choi J,Joseph L,Pilote L.Obesity and C-reactive protein in various populations:A systematic review and meta-analysis[J].Obes Rev,2013,14(3):232-244.
[35]Oh HY,Seo SS,Kong JS,et al.Association between obesity and cervical microflora dominated by Lactobacillus iners in Korean women[J].J Clin Microbiol,2015,53(10):3304-3309.
[36]Dossus L,Lukanova A,Rinaldi S,et al.Hormonal,metabolic,and inflammatory profiles and endometrial cancer risk within the EPIC cohort-A factor analysis[J].Am J Epidemiol,2013,177(8):787-99.
[37]Yang TK,Chung CJ,Chung SD,et al.Risk of endometrial cancer in women with pelvic inflammatory disease:A nationwide population-based retrospective cohort study[J].Medicine(Baltimore),2015,94(34):e1278..
[38]Hunn J,Rodriguez GC.Ovarian cancer:Etiology,risk factors,and epidemiology[J].Clin Obstet Gynecol,2012,55(1):3-23.
[39]Rosa MI,Silva GD,de Azedo Sim7es PW,et al.The prevalence of human papillomavirus in ovarian cancer:A systematic review[J].Int J Gynecol Cancer,2013,23(3):437-441.
[40]Shanmughapriya S,Senthilkumar G,Vinodhini K,et al.Viral and bacterial aetiologies of epithelial ovarian cancer[J].Eur JClin Microbiol Infect Dis,2012,31(9):2311-2317.
[41]Ingerslev K,Hogdall E,Schnack TH,et al.The potential role of infectious agents and pelvic inflammatory disease in ovarian carcinogenesis[J].Infect Agents Cancer,2017,12:25.
[42]Francescone R,Hou V,Grivennikov SI.Microbiome,inflammation,and cancer[J].Cancer J,2014,20(3):181-189.
[43]Shan W,Liu J.Inflammation:A hidden path to breaking the spell of ovarian cancer[J].Cell Cycle,2009,8(19):3107-3111.
[44]Risch HA,Howe GR.Pelvic inflammatory disease and the risk of epithelial ovarian cancer[J].Cancer Epidemiol Biomarkers Prev,1995,4(5):447-551.
[45]Lin HW,Tu YY,Lin SY,et al.Risk of ovarian cancer in women with pelvic inflammatory disease:A population-based study[J].Lancet Oncol,2011,12(9):900-904.
[46]Schwabe RF,Jobin C.The microbiome and cancer[J].Nat Rev Cancer,2013,13(11):800-812.
[47]Bultman SJ.Emerging roles of the microbiome in cancer[J].Carcinogenesis,2014,35(2):249-255.
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