Cross-Cancer Genome-Wide Analysis of Lung, Ovary, Breast, Prostate, and Colorectal Cancer Reveals Novel Pleiotropic Associations
Gordon Fehringer(Lunenfeld-Tanenbaum Research Institute), Peter Kraft(Massachusetts Department of Public Health), Paul D.P. Pharoah(University of Cambridge), Rosalind A. Eeles(Institute of Cancer Research), Nilanjan Chatterjee(National Cancer Institute), Fredrick R. Schumacher(University of Southern California), Joellen M. Schildkraut(University of Virginia), Sara Lindström(Massachusetts Department of Public Health), Paul Brennan(Centre international de recherche sur le cancer), Heike Bickeböller(Universitätsmedizin Göttingen), Richard S. Houlston(Institute of Cancer Research), Maria Teresa Landi(National Cancer Institute), Neil E. Caporaso(National Cancer Institute), Angela Risch(University of Salzburg), Ali Amin Al Olama(Bridge University), Sonja I. Berndt(National Cancer Institute), Edward L. Giovannucci(Massachusetts Department of Public Health), Henrik Grönberg(Svenska Örtmedicinska Institute), Zsofia Kote‐Jarai(Institute of Cancer Research), Jing Ma(Brigham and Women's Hospital), Kenneth Muir(University of Manchester), Meir J. Stampfer(Boston Medical Center), Victoria L. Stevens(American Cancer Society), Fredrik Wiklund(Svenska Örtmedicinska Institute), Walter C. Willett(Massachusetts Department of Public Health), Ellen L. Goode(Mayo Clinic), Jennifer B. Permuth(Moffitt Cancer Center), Harvey A. Risch(New Haven Public Schools), Brett M. Reid(Moffitt Cancer Center), Stéphane Bezieau(Génétique Médicale & Génomique Fonctionelle), Hermann Brenner(German Cancer Research Center), Andrew T. Chan(Massachusetts General Hospital), Jenny Chang‐Claude(German Cancer Research Center), Thomas J. Hudson(Ontario Institute for Cancer Research), Jonathan K. Kocarnik(Fred Hutch Cancer Center), Polly A. Newcomb(Fred Hutch Cancer Center), Robert E. Schoen(University of Pittsburgh Medical Center), Martha L. Slattery(Utah Department of Health), Emily White(Fred Hutch Cancer Center), Muriel A. Adank(Amsterdam UMC Location Vrije Universiteit Amsterdam), Habibul Ahsan(University of Illinois Chicago), Kristiina Aittomäki(Helsinki University Hospital), Laura Baglietto(The University of Melbourne), Carl Blomquist(Helsinki University Hospital), Federico Canzian(German Cancer Research Center), Kamila Czene(Svenska Örtmedicinska Institute), Isabel dos‐Santos‐Silva(London School of Hygiene & Tropical Medicine), A. Heather Eliassen(Boston Medical Center), Jonine D. Figueroa(National Cancer Institute), Dieter Flesch‐Janys(Universität Hamburg), Olivia Fletcher(Institute of Cancer Research), Montserrat García‐Closas(National Cancer Institute), Mia M. Gaudet(American Cancer Society), Nichola Johnson(Institute of Cancer Research), Per Hall(Svenska Örtmedicinska Institute), Aditi Hazra(Boston Medical Center), Rebecca Hein(German Cancer Research Center), Albert Hofman(Erasmus MC), John L. Hopper(Melbourne Health), Astrid Irwanto(Singapore Institute of Technology), Mattias Johansson(Centre international de recherche sur le cancer), Rudolf Kaaks(German Cancer Research Center), Muhammad G. Kibriya(University of Illinois Chicago), Peter Lichtner(Helmholtz Zentrum München), Jianjun Liu(Singapore Institute of Technology), Eiliv Lund(UiT The Arctic University of Norway), Enes Makalic(Melbourne Health), Alfons Meindl(Technical University of Munich), Bertram Müller‐Myhsok(Max Planck Institute of Psychiatry), Taru Muranen(Helsinki University Hospital), Heli Nevanlinna(Helsinki University Hospital), Petra H. Peeters(University Medical Center Utrecht), Julian Peto(London School of Hygiene & Tropical Medicine), Ross L. Prentice(Fred Hutch Cancer Center), Nazneen Rahman(Institute of Cancer Research), María‐José Sánchez(Universidad de Granada), Daniel F. Schmidt(Melbourne Health), Rita K. Schmutzler(University of Cologne), Melissa C. Southey(The University of Melbourne), Rulla M. Tamimi(Boston Medical Center), Ruth C. Travis(University of Oxford), Clare Turnbull(Institute of Cancer Research), André G. Uitterlinden(Erasmus MC), Zhaoming Wang(National Cancer Institute), Alice S. Whittemore(Stanford University), Xiaohong R. Yang(National Cancer Institute), Wei Zheng(Vanderbilt University), Daniel D. Buchanan(The University of Melbourne), Graham Casey(University of Southern California), David V. Conti(University of Southern California), Christopher K. Edlund(University of Southern California), Steven Gallinger(Lunenfeld-Tanenbaum Research Institute), Robert W. Haile(Stanford University), Mark A. Jenkins(The University of Melbourne), Loı̈c Le Marchand(Cancer Center of Hawaii), Li Li(Harvard University), Noralene M. Lindor(Mayo Clinic in Arizona), Stephanie L. Schmit(University of Southern California), Stephen N. Thibodeau(Mayo Clinic), Michael O. Woods(Memorial University of Newfoundland), Þórunn Rafnar(deCODE Genetics (Iceland)), Jūlı́us Guðmundsson(deCODE Genetics (Iceland)), Simon Stacey(deCODE Genetics (Iceland)), Kāri Stefánsson(deCODE Genetics (Iceland)), Patrick Sulem(deCODE Genetics (Iceland)), Y. Ann Chen(Moffitt Cancer Center), Jonathan P. Tyrer(University of Cambridge), David C. Christiani(Massachusetts Department of Public Health), Yongyue Wei(Massachusetts Department of Public Health), Hongbing Shen(Xijing University), Zhibin Hu(Xijing University), Xiao‐Ou Shu(Vanderbilt University), Kouya Shiraishi(National Cancer Research Institute), Atsushi Takahashi(RIKEN Center for Integrative Medical Sciences), Yohan Bossé(Institut universitaire de cardiologie et de pneumologie de Québec), Ma’en Obeidat(St. Paul's Hospital), David C. Nickle(Merck & Co., Inc., Rahway, NJ, USA (United States)), Wim Timens(University Medical Center Groningen), Matthew L. Freedman(Dana-Farber Cancer Institute), Qiyuan Li(Xiamen University), Daniela Seminara(National Cancer Institute), Stephen J. Chanock(National Cancer Institute), Jian Gong(Fred Hutch Cancer Center), Ulrike Peters(Fred Hutch Cancer Center), Stephen B. Gruber(University of Southern California), Christopher I. Amos(Dartmouth College), Thomas A. Sellers(Moffitt Cancer Center), Douglas F. Easton(University of Cambridge), David J. Hunter(Massachusetts Department of Public Health), Christopher A. Haiman(University of Southern California), Brian E. Henderson(University of Southern California), Rayjean J. Hung(Lunenfeld-Tanenbaum Research Institute)
Cited by 119Open Access
Abstract
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 at CDKN2B-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. Cancer Res; 76(17); 5103-14. ©2016 AACR.
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