A genome-wide association study identifies two new cervical cancer susceptibility loci at 4q12 and 17q12

被引：128

作者：

Shi, Yongyong ^{[1
,2
,3
,4
,5
]}

Li, Li ^{[6
]}

Hu, Zhibin ^{[7
,8
]}

Li, Shuang ^{[1
]}

Wang, Shixuan ^{[1
]}

Liu, Jihong ^{[9
]}

Wu, Chen ^{[10
,11
]}

He, Lin ^{[2
,3
,4
,5
]}

Zhou, Jianfeng ^{[12
]}

Li, Zhiqiang ^{[2
,3
,4
,5
]}

Hu, Ting ^{[1
]}

Chen, Yile ^{[13
]}

Jia, Yao ^{[1
]}

Wang, Shaoshuai ^{[1
]}

Wu, Li ^{[13
]}

Cheng, Xiaodong ^{[14
]}

Yang, Zhijun ^{[6
]}

Yang, Ru ^{[1
]}

Li, Xiong ^{[1
]}

Huang, Kecheng ^{[1
]}

Zhang, Qinghua ^{[1
]}

Zhou, Hang ^{[1
]}

Tang, Fangxu ^{[1
]}

Chen, Zhilan ^{[1
]}

Shen, Jian ^{[1
]}

Jiang, Jie ^{[7
,8
]}

Ding, Hu ^{[12
]}

Xing, Hui ^{[15
]}

Zhang, Shulan ^{[16
]}

Qu, Pengpeng ^{[17
]}

Song, Xiaojie ^{[18
]}

Lin, Zhongqiu ^{[19
]}

Deng, Dongrui ^{[1
]}

Xi, Ling ^{[1
]}

Lv, Weiguo ^{[14
]}

Han, Xiaobing ^{[20
]}

Tao, Guangshi ^{[21
]}

Yan, Lixing ^{[22
]}

Han, Zhedong ^{[22
]}

Li, Zhuang ^{[6
]}

Miao, Xiaoping ^{[23
]}

Pan, Shandong ^{[7
,8
]}

Shen, Yuanming ^{[14
]}

Wang, Hui ^{[1
]}

Liu, Dan ^{[1
]}

Gong, Ee ^{[1
]}

Li, Zheng ^{[9
]}

Zhou, Limei ^{[17
]}

Luan, Xiaomei ^{[16
]}

Wang, Chuping ^{[24
]}

机构：

[1] Huazhong Univ Sci & Technol, Tongji Med Coll, Tongji Hosp, Dept Obstet & Gynecol, Wuhan 430074, Hubei, Peoples R China

[2] Shanghai Jiao Tong Univ, Bio X Inst, Key Lab Genet Dev & Neuropsychiat Disorders, Minist Educ, Shanghai 200030, Peoples R China

[3] Shanghai Genome Pilot Inst Genom Hlth, Shanghai, Peoples R China

[4] Shanghai Genome Pilot Inst Human Hlth, Shanghai, Peoples R China

[5] Changning Mental Hlth Ctr, Shanghai, Peoples R China

[6] Guangxi Prov Tumor Hosp, Dept Gynecol Oncol, Nanning, Peoples R China

[7] Nanjing Med Univ, State Key Lab Reprod Med, Nanjing, Jiangsu, Peoples R China

[8] Nanjing Med Univ, Sch Publ Hlth, Jiangsu Key Lab Canc Biomarkers Prevent & Treatme, Nanjing, Jiangsu, Peoples R China

[9] Sun Yat Sen Univ, Ctr Canc, Dept Gynecol Oncol, Guangzhou 510275, Guangdong, Peoples R China

[10] Chinese Acad Med Sci, Canc Inst & Hosp, State Key Lab Mol Oncol, Beijing 100730, Peoples R China

[11] Peking Union Med Coll, Beijing 100021, Peoples R China

[12] Huazhong Univ Sci & Technol, Tongji Med Coll, Tongji Hosp, Dept Internal Med, Wuhan 430074, Hubei, Peoples R China

[13] Hunan Prov Tumor Hosp, Dept Gynecol Oncol, Changsha, Hunan, Peoples R China

[14] Zhejiang Univ, Sch Med, Womens Hosp, Hangzhou 310003, Zhejiang, Peoples R China

[15] Hubei Univ Arts & Sci, Affiliated Hosp 1, Xiangyang Cent Hosp, Dept Obstet & Gynecol, Xiangyang, Peoples R China

[16] China Med Univ, Shengjing Hosp, Dept Obstet & Gynecol, Shenyang, Peoples R China

[17] Tianjin Cent Hosp Gynecol & Obstet, Tianjin, Peoples R China

[18] Wuhan Med Ctr Women & Children, Wuhan, Peoples R China

[19] Sun Yat Sen Univ, Affiliated Hosp 2, Dept Gynecol Oncol, Guangzhou 510275, Guangdong, Peoples R China

[20] Xi An Jiao Tong Univ, Sch Med, Affiliated Hosp 1, Dept Obstet & Gynecol, Xian 710049, Peoples R China

[21] Cent South Univ, Xiangya Hosp 2, Dept Obstet & Gynecol, Changsha, Hunan, Peoples R China

[22] Minist Hlth, Key Lab Blood Safety, Blood Ctr Zhejiang Prov, Hangzhou, Zhejiang, Peoples R China

[23] Huazhong Univ Sci & Technol, Tongji Med Coll, Dept Epidemiol & Biostat, Minist Educ,Key Lab Environm & Hlth,Sch Publ Hlth, Wuhan 430074, Hubei, Peoples R China

[24] Huangshi Cent Hosp, Dept Obstet & Gynecol, Huangshi, Peoples R China

[25] Xiaogan Cent Hosp, Dept Obstet & Gynecol, Xiaogan, Peoples R China

[26] Hosp Fudan Univ, Dept Gynecol Obstet & Gynecol, Shanghai, Peoples R China

[27] Peoples Hosp Shenzhen, Dept Gynecol & Obstet, Shenzhen, Peoples R China

[28] Nantong Tumor Hosp, Nantong, Peoples R China

[29] Guangxi Maternal & Child Hlth Hosp, Dept Obstet & Gynecol, Nanning, Peoples R China

[30] Nanjing Med Univ, Nanjing Matern & Child Hlth Hosp, Nanjing, Jiangsu, Peoples R China

[31] 181 Hosp Peoples Liberat Army, Maternal & Child Ctr, Guilin, Peoples R China

[32] Peoples Hosp Guangxi Zhuang Autonomous Reg, Dept Obstet & Gynecol, Nanning, Peoples R China

[33] Guangxi Univ Med Sci, Affiliated Hosp 1, Dept Obstet & Gynecol, Nanning, Peoples R China

[34] Liuzhou Worker Hosp, Dept Obstet & Gynecol, Liuzhou, Peoples R China

[35] Peoples Hosp Liuzhou, Dept Obstet & Gynecol, Liuzhou, Peoples R China

[36] Youjiang Med Coll Nationalities, Dept Obstet & Gynecol, Affiliated Hosp, Baise, Peoples R China

[37] Red Cross Hosp Yulin City, Dept Obstet & Gynecol, Yulin, Peoples R China

[38] Shanghai Inst Mental Hlth, Shanghai, Peoples R China

[39] Huazhong Univ Sci & Technol, Tongji Med Coll, Union Hosp, Dept Obstet & Gynecol, Wuhan 430074, Hubei, Peoples R China

[40] First Peoples Hosp Jingzhou City, Dept Obstet & Gynecol, Jinzhou, Peoples R China

[41] Taihe Hosp Shiyan, Dept Gynecol Oncol, Shiyan, Peoples R China

[42] Shanghai Jiao Tong Univ, Dept Obstet & Gynecol, Renji Hosp, Sch Med, Shanghai 200030, Peoples R China

[43] Chinese Acad Med Sci, Dept Obstet & Gynecol, Peking Union Med Coll Hosp, Peking Union Med Coll, Beijing 100730, Peoples R China

来源：

NATURE GENETICS | 2013年 / 45卷 / 08期

基金：

中国国家自然科学基金;

关键词：

T-CELL-ACTIVATION; NEF; COMPLEX; PAPILLOMAVIRUSES; STRATIFICATION; PROGRESSION; EXPRESSION; IMPUTATION; REGRESSION; GASDERMIN;

D O I：

10.1038/ng.2687

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

To identify new genetic risk factors for cervical cancer, we conducted a genome-wide association study in the Han Chinese population. The initial discovery set included 1,364 individuals with cervical cancer (cases) and 3,028 female controls, and we selected a 'stringently matched samples' subset (829 cases and 990 controls) from the discovery set on the basis of principal component analysis; the follow-up stages included two independent sample sets (1,824 cases and 3,808 controls for follow-up 1 and 2,343 cases and 3,388 controls for follow-up 2). We identified strong evidence of associations between cervical cancer and two new loci: 4q12 (rs13117307, P-combined,P- stringently matched = 9.69 x 10(-9), per-allele odds ratio (OR)(stringently matched) = 1.26) and 17q12 (rs8067378, P-combined,P- stringently matched = 2.00 x 10(-8), per-allele ORstringently matched = 1.18). We additionally replicated an association between HLA-DPB1 and HLA-DPB2 (HLA-DPB1/2) at 6p21.32 and cervical cancer (rs4282438, Pcombined, stringently matched = 4.52 x 10(-27), per-allele ORstringently matched = 0.75). Our findings provide new insights into the genetic etiology of cervical cancer.

引用

页码：918 / U262

页数：7

共 43 条

[1] Worldwide burden of cervical cancer in 2008 [J].

Arbyn, M. ;

Castellsague, X. ;

de Sanjose, S. ;

Bruni, L. ;

Saraiya, M. ;

Bray, F. ;

Ferlay, J. .

ANNALS OF ONCOLOGY, 2011, 22 (12) :2675-2686

[2] The epidemiology of human papillomavirus infections [J].

Baseman, JG ;

Koutsky, LA .

JOURNAL OF CLINICAL VIROLOGY, 2005, 32 :S16-S24

[3] Differential expression and localisation of gasdermin-like (GSDML), a novel member of the cancer-associated GSDMDC protein family, in neoplastic and non-neoplastic gastric, hepatic, and colon tissues [J].

Carl-Mcgrath, Stacy ;

Schneider-Stock, Regine ;

Ebert, Matthias ;

Roecken, Christoph .

PATHOLOGY, 2008, 40 (01) :13-24

[4]

CHEN TM, 1993, CANCER RES, V53, P1167

[5] Persistence and load of high-risk hpv are predictors for development of high-grade cervical lesions:: A longitudinal French cohort study [J].

Dalstein, W ;

Riethmuller, D ;

Prétet, JL ;

Carval, KL ;

Sautière, JL ;

Carbillet, JP ;

Kantelip, B ;

Schaal, JP ;

Mougin, C .

INTERNATIONAL JOURNAL OF CANCER, 2003, 106 (03) :396-403

[6] A high-resolution HLA and SNP haplotype map for disease association studies in the extended human MHC [J].

de Bakker, Paul I. W. ;

McVean, Gil ;

Sabeti, Pardis C. ;

Miretti, Marcos M. ;

Green, Todd ;

Marchini, Jonathan ;

Ke, Xiayi ;

Monsuur, Alienke J. ;

Whittaker, Pamela ;

Delgado, Marcos ;

Morrison, Jonathan ;

Richardson, Angela ;

Walsh, Emily C. ;

Gao, Xiaojiang ;

Galver, Luana ;

Hart, John ;

Hafler, David A. ;

Pericak-Vance, Margaret ;

Todd, John A. ;

Daly, Mark J. ;

Trowsdale, John ;

Wijmenga, Cisca ;

Vyse, Tim J. ;

Beck, Stephan ;

Murray, Sarah Shaw ;

Carrington, Mary ;

Gregory, Simon ;

Deloukas, Panos ;

Rioux, John D. .

NATURE GENETICS, 2006, 38 (10) :1166-1172

[7] Practical aspects of imputation-driven meta-analysis of genome-wide association studies [J].

de Bakker, Paul I. W. ;

Ferreira, Manuel A. R. ;

Jia, Xiaoming ;

Neale, Benjamin M. ;

Raychaudhuri, Soumya ;

Voight, Benjamin F. .

HUMAN MOLECULAR GENETICS, 2008, 17 :R122-R128

[8] Anti-tumor CD8+ T cell immunity elicited by HIV-1-based virus-like particles incorporating HPV-16 E7 protein [J].

Di Bonito, Paola ;

Grasso, Felicia ;

Mochi, Stefania ;

Petrone, Linda ;

Fanales-Belasio, Emanuele ;

Mei, Arianna ;

Cesolini, Armando ;

Laconi, Giuseppe ;

Conrad, Heinke ;

Bernhard, Helga ;

Dembek, Claudia J. ;

Cosma, Antonio ;

Santini, Stefano M. ;

Lapenta, Caterina ;

Donati, Simona ;

Muratori, Claudia ;

Giorgi, Colomba ;

Federico, Maurizio .

VIROLOGY, 2009, 395 (01) :45-55

[9] Nef is physically recruited into the immunological synapse and potentiates T cell activation early after TCR engagement [J].

Fenard, D ;

Yonemoto, W ;

de Noronha, C ;

Cavrois, M ;

Williams, SA ;

Greene, WC .

JOURNAL OF IMMUNOLOGY, 2005, 175 (09) :6050-6057

[10] Assessing the impact of population stratification on genetic association studies [J].

Freedman, ML ;

Reich, D ;

Penney, KL ;

McDonald, GJ ;

Mignault, AA ;

Patterson, N ;

Gabriel, SB ;

Topol, EJ ;

Smoller, JW ;

Pato, CN ;

Pato, MT ;

Petryshen, TYL ;

Kolonel, LN ;

Lander, ES ;

Sklar, P ;

Henderson, B ;

Hirschhorn, JN ;

Altshuler, D .

NATURE GENETICS, 2004, 36 (04) :388-393

← 1 2 3 4 5 →