Cross-Cancer Genome-Wide Analysis of Lung, Ovary, Breast, Prostate, and Colorectal Cancer Reveals Novel Pleiotropic Associations

被引：84

作者：

Fehringer, Gordon ^{[1
]}

Kraft, Peter ^{[2
]}

Pharoah, Paul D. ^{[3
]}

Eeles, Rosalind A. ^{[4
]}

Chatterjee, Nilanjan ^{[5
]}

Schumacher, Fredrick R. ^{[6
]}

Schildkraut, Joellen M. ^{[7
]}

Lindstrom, Sara ^{[2
]}

Brennan, Paul ^{[8
]}

Bickeboller, Heike ^{[9
]}

Houlston, Richard S. ^{[4
]}

Landi, Maria Teresa ^{[5
]}

Caporaso, Neil ^{[5
]}

Risch, Angela ^{[10
,11
,12
]}

Al Olama, Ali Amin ^{[13
]}

Berndt, Sonja I. ^{[5
]}

Giovannucci, Edward L. ^{[2
]}

Gronberg, Henrik ^{[14
]}

Kote-Jarai, Zsofia ^{[4
]}

Ma, Jing ^{[15
]}

Muir, Kenneth ^{[16
,17
]}

Stampfer, Meir J. ^{[15
]}

Stevens, Victoria L. ^{[18
]}

Wiklund, Fredrik ^{[14
]}

Willett, Walter C. ^{[2
]}

Goode, Ellen L. ^{[19
]}

Permuth, Jennifer B. ^{[20
]}

Risch, Harvey A. ^{[21
]}

Reid, Brett M. ^{[20
]}

Bezieau, Stephane ^{[22
]}

Brenner, Hermann ^{[23
,24
,25
]}

Chan, Andrew T. ^{[26
]}

Chang-Claude, Jenny ^{[27
,28
]}

Hudson, Thomas J. ^{[29
]}

Kocarnik, Jonathan K. ^{[30
]}

Newcomb, Polly A. ^{[30
]}

Schoen, Robert E. ^{[31
]}

Slattery, Martha L. ^{[32
]}

White, Emily ^{[30
]}

Adank, Muriel A. ^{[33
]}

Ahsan, Habibul ^{[34
]}

Aittomaki, Kristiina ^{[35
,36
]}

Baglietto, Laura ^{[37
]}

Blomquist, Carl ^{[35
,36
]}

Canzian, Federico ^{[38
]}

Czene, Kamila ^{[14
]}

dos-Santos-Silva, Isabel ^{[39
]}

Eliassen, A. Heather ^{[2
,15
]}

Figueroa, Jonine D. ^{[5
]}

Flesch-Janys, Dieter ^{[40
]}

机构：

[1] Mt Sinai Hosp, Lunenfeld Tanenbaum Res Inst, 60 Murray St, Toronto, ON M5T 3L9, Canada

[2] Harvard TH Chan Sch Publ Hlth, Boston, MA USA

[3] Univ Cambridge, Cambridge, England

[4] Inst Canc Res, London, England

[5] NCI, Bethesda, MD 20892 USA

[6] Univ So Calif, Los Angeles, CA USA

[7] Univ Virginia, Charlottesville, VA USA

[8] Int Agcy Res Canc, Lyon, France

[9] Univ Gottingen, Sch Med, Gottingen, Germany

[10] Salzburg Univ, Div Canc Genet Epigenet, Dept Mol Biol, Salzburg, Austria

[11] DKFZ German Canc Res Ctr, Div Epigenom & Canc Risk Factors, Heidelberg, Germany

[12] German Ctr Lung Res DZL, Translat Lung Res Ctr Heidelberg TLRCH, Heidelberg, Germany

[13] Univ Cambridge, Cambridge, England

[14] Karolinska Inst, Stockholm, Sweden

[15] Harvard Univ, Sch Med, Boston, MA USA

[16] Univ Manchester, Manchester, Lancs, England

[17] Univ Warwick, Coventry, W Midlands, England

[18] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30329 USA

[19] Mayo Clin, Rochester, MN USA

[20] Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA

[21] Yale Univ, Sch Publ Hlth, New Haven, CT USA

[22] Serv Genet Med, Nantes, France

[23] German Canc Res Ctr, Div Clin Epidemiol & Aging Res, Heidelberg, Germany

[24] German Canc Res Ctr, Div Prevent Oncol, Heidelberg, Germany

[25] German Canc Res Ctr, German Canc Consortium DKTK, Heidelberg, Germany

[26] Massachusetts Gen Hosp, Boston, MA 02114 USA

[27] Natl Ctr Tumor Dis, Heidelberg, Germany

[28] German Canc Res Ctr, Heidelberg, Germany

[29] Ontario Inst Canc Res, Toronto, ON, Canada

[30] Fred Hutchinson Canc Res Ctr, 1124 Columbia St, Seattle, WA 98104 USA

[31] Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA

[32] Univ Utah, Hlth Sci Ctr, Salt Lake City, UT USA

[33] Vrije Univ Amsterdam, Med Ctr, Amsterdam, Netherlands

[34] Univ Chicago, Chicago, IL USA

[35] Univ Helsinki, Helsinki, Finland

[36] Univ Helsinki, Cent Hosp, Helsinki, Finland

[37] Univ Melbourne, Melbourne, Vic, Australia

[38] German Canc Res Ctr, Gen Epidemiol Grp, Heidelberg, Germany

[39] London Sch Hyg & Trop Med, Dept Noncommunicable Dis Epidemiol, London, England

[40] Univ Med Ctr HamburgEppendorf, Hamburg, Germany

[41] Breakthrough Res Ctr, Inst Canc Res, London, England

[42] German Canc Res Ctr DKFZ Heidelberg, Div Canc Epidemiol, Heidelberg, Germany

[43] Univ Cologne, Inst Med Stat Informat & Epidemiol, Cologne, Germany

[44] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands

[45] Univ Melbourne, Melbourne Sch Populat Hlth, Melbourne, Vic, Australia

[46] Genome Inst Singapore, Singapore, Singapore

[47] Umea Univ, Dept Biobank Res, Umea, Sweden

[48] German Res Ctr Environm Hlth, Neuherberg, Germany

[49] UiT Arctic Univ Norway, Inst Community Med, Tromso, Norway

[50] Tech Univ Munich, Munich, Germany

来源：

CANCER RESEARCH | 2016年 / 76卷 / 17期

基金：

英国医学研究理事会;

关键词：

SUSCEPTIBILITY LOCI; IDENTIFIES; 2; GENETIC POLYMORPHISMS; AGGRESSIVE PROSTATE; AFRICAN ANCESTRY; COMMON VARIANTS; GASTRIC-CANCER; CELL CARCINOMA; RISK LOCI; METAANALYSIS;

D O I：

10.1158/0008-5472.CAN-15-2980

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Identifying genetic variants with pleiotropic associations can uncover common pathways influencing multiple cancers. We took a two-stage approach to conduct genome-wide association studies for lung, ovary, breast, prostate, and colorectal cancer from the GAME-ON/GECCO Network (61,851 cases, 61,820 controls) to identify pleiotropic loci. Findings were replicated in independent association studies (55,789 cases, 330,490 controls). We identified a novel pleiotropic association at 1q22 involving breast and lung squamous cell carcinoma, with eQTL analysis showing an association with ADAM15/THBS3 gene expression in lung. We also identified a known breast cancer locus CASP8/ALS2CR12 associated with prostate cancer, a known cancer locus atCDKN2B-AS1 with different variants associated with lung adenocarcinoma and prostate cancer, and confirmed the associations of a breast BRCA2 locus with lung and serous ovarian cancer. This is the largest study to date examining pleiotropy across multiple cancer-associated loci, identifying common mechanisms of cancer development and progression. (C) 2016 AACR.

引用

页码：5103 / 5114

页数：12

共 47 条

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← 1 2 3 4 5 →

共 47 条

[1] Genotypic variants at 2q33 and risk of esophageal squamous cell carcinoma in China: a meta-analysis of genome-wide association studies [J].

Abnet, Christian C. ;

Wang, Zhaoming ;

Song, Xin ;

Hu, Nan ;

Zhou, Fu-You ;

Freedman, Neal D. ;

Li, Xue-Min ;

Yu, Kai ;

Shu, Xiao-Ou ;

Yuan, Jian-Min ;

Zheng, Wei ;

Dawsey, Sanford M. ;

Liao, Linda M. ;

Lee, Maxwell P. ;

Ding, Ti ;

Qiao, You-Lin ;

Gao, Yu-Tang ;

Koh, Woon-Puay ;

Xiang, Yong-Bing ;

Tang, Ze-Zhong ;

Fan, Jin-Hu ;

Chung, Charles C. ;

Wang, Chaoyu ;

Wheeler, William ;

Yeager, Meredith ;

Yuenger, Jeff ;

Hutchinson, Amy ;

Jacobs, Kevin B. ;

Giffen, Carol A. ;

Burdett, Laurie ;

Fraumeni, Joseph F., Jr. ;

Tucker, Margaret A. ;

Chow, Wong-Ho ;

Zhao, Xue-Ke ;

Li, Jiang-Man ;

Li, Ai-Li ;

Sun, Liang-Dan ;

Wei, Wu ;

Li, Ji-Lin ;

Zhang, Peng ;

Li, Hong-Lei ;

Cui, Wen-Yan ;

Wang, Wei-Peng ;

Liu, Zhi-Cai ;

Yang, Xia ;

Fu, Wen-Jing ;

Cui, Ji-Li ;

Lin, Hong-Li ;

Zhu, Wen-Liang ;

Liu, Min .

HUMAN MOLECULAR GENETICS, 2012, 21 (09) :2132-2141

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Al Olama, Ali Amin ;

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Berndt, Sonja I. ;

Conti, David V. ;

Schumacher, Fredrick ;

Han, Ying ;

Benlloch, Sara ;

Hazelett, Dennis J. ;

Wang, Zhaoming ;

Saunders, Ed ;

Leongamornlert, Daniel ;

Lindstrom, Sara ;

Jugurnauth-Little, Sara ;

Dadaev, Tokhir ;

Tymrakiewicz, Malgorzata ;

Stram, Daniel O. ;

Rand, Kristin ;

Wan, Peggy ;

Stram, Alex ;

Sheng, Xin ;

Pooler, Loreall C. ;

Park, Karen ;

Xia, Lucy ;

Tyrer, Jonathan ;

Kolonel, Laurence N. ;

Le Marchand, Loic ;

Hoover, Robert N. ;

Machiela, Mitchell J. ;

Yeager, Merideth ;

Burdette, Laurie ;

Chung, Charles C. ;

Hutchinson, Amy ;

Yu, Kai ;

Goh, Chee ;

Ahmed, Mahbubl ;

Govindasami, Koveela ;

Guy, Michelle ;

Tammela, Teuvo L. J. ;

Auvinen, Anssi ;

Wahlfors, Tlina ;

Schleutker, Johanna ;

Visakorpi, Tapio ;

Leinonen, Katri A. ;

Xu, Jianfeng ;

Aly, Markus ;

Donovan, Jenny ;

Travis, Ruth C. ;

Key, Tim J. ;

Siddiq, Afshan ;

Canzian, Federico .

NATURE GENETICS, 2014, 46 (10) :1103-1109

[3] Shared common variants in prostate cancer and blood lipids [J].

Andreassen, Ole A. ;

Zuber, Verena ;

Thompson, Wesley K. ;

Schork, Andrew J. ;

Bettella, Francesco ;

Djurovic, Srdjan ;

Desikan, Rahul S. ;

Mills, Ian G. ;

Dale, Anders M. .

INTERNATIONAL JOURNAL OF EPIDEMIOLOGY, 2014, 43 (04) :1205-1214

[4] Second hand smoke, age of exposure and tung cancer risk [J].

Asomaning, Kofi ;

Miller, David P. ;

Liu, Geoffrey ;

Wain, John C. ;

Lynch, Thomas J. ;

Su, Li ;

Christiani, David C. .

LUNG CANCER, 2008, 61 (01) :13-20

[5] Genome-wide association study identifies three new melanoma susceptibility loci [J].

Barrett, Jennifer H. ;

Iles, Mark M. ;

Harland, Mark ;

Taylor, John C. ;

Aitken, Joanne F. ;

Andresen, Per Arne ;

Akslen, Lars A. ;

Armstrong, Bruce K. ;

Avril, Marie-Francoise ;

Azizi, Esther ;

Bakker, Bert ;

Bergman, Wilma ;

Bianchi-Scarra, Giovanna ;

Bressac-de Paillerets, Brigitte ;

Calista, Donato ;

Cannon-Albright, Lisa A. ;

Corda, Eve ;

Cust, Anne E. ;

Debniak, Tadeusz ;

Duffy, David ;

Dunning, Alison M. ;

Easton, Douglas F. ;

Friedman, Eitan ;

Galan, Pilar ;

Ghiorzo, Paola ;

Giles, Graham G. ;

Hansson, Johan ;

Hocevar, Marko ;

Hoeiom, Veronica ;

Hopper, John L. ;

Ingvar, Christian ;

Janssen, Bart ;

Jenkins, Mark A. ;

Joensson, Goeran ;

Kefford, Richard F. ;

Landi, Giorgio ;

Landi, Maria Teresa ;

Lang, Julie ;

Lubinski, Jan ;

Mackie, Rona ;

Malvehy, Josep ;

Martin, Nicholas G. ;

Molven, Anders ;

Montgomery, Grant W. ;

van Nieuwpoort, Frans A. ;

Novakovic, Srdjan ;

Olsson, Hakan ;

Pastorino, Lorenza ;

Puig, Susana ;

Puig-Butille, Joan Anton .

NATURE GENETICS, 2011, 43 (11) :1108-U98

[6] A Subset-Based Approach Improves Power and Interpretation for the Combined Analysis of Genetic Association Studies of Heterogeneous Traits [J].

Bhattacharjee, Samsiddhi ;

Rajaraman, Preetha ;

Jacobs, Kevin B. ;

Wheeler, William A. ;

Melin, Beatrice S. ;

Hartge, Patricia ;

Yeager, Meredith ;

Chung, Charles C. ;

Chanock, Stephen J. ;

Chatterjee, Nilanjan .

AMERICAN JOURNAL OF HUMAN GENETICS, 2012, 90 (05) :821-835

[7] Genome-wide association analysis in East Asians identifies breast cancer susceptibility loci at 1q32.1, 5q14.3 and 15q26.1 [J].

Cai, Qiuyin ;

Zhang, Ben ;

Sung, Hyuna ;

Low, Siew-Kee ;

Kweon, Sun-Seog ;

Lu, Wei ;

Shi, Jiajun ;

Long, Jirong ;

Wen, Wanqing ;

Choi, Ji-Yeob ;

Noh, Dong-Young ;

Shen, Chen-Yang ;

Matsuo, Keitaro ;

Teo, Soo-Hwang ;

Kim, Mi Kyung ;

Khoo, Ui Soon ;

Iwasaki, Motoki ;

Hartman, Mikael ;

Takahashi, Atsushi ;

Ashikawa, Kyota ;

Matsuda, Koichi ;

Shin, Min-Ho ;

Park, Min Ho ;

Zheng, Ying ;

Xiang, Yong-Bing ;

Ji, Bu-Tian ;

Park, Sue K. ;

Wu, Pei-Ei ;

Hsiung, Chia-Ni ;

Ito, Hidemi ;

Kasuga, Yoshio ;

Kang, Peter ;

Mariapun, Shivaani ;

Ahn, Sei Hyun ;

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