Cross-Cancer Genome-Wide Analysis of Lung, Ovary, Breast, Prostate, and Colorectal Cancer Reveals Novel Pleiotropic Associations
Authors: Gordon Fehringer, Peter Kraft, Paul D. Pharoah, Rosalind A. Eeles, Nilanjan Chatterjee, Fredrick R. Schumacher, Joellen M. Schildkraut, Sara Lindström, Paul Brennan, Heike Bickeböller, Richard S. Houlston, Maria Teresa Landi, Neil Caporaso, Angela Risch, Ali Amin Al Olama, Sonja I. Berndt, Edward L. Giovannucci, Henrik Grönberg, Zsofia Kote-Jarai, Jing Ma, Kenneth Muir, Meir J. Stampfer, Victoria L. Stevens, Fredrik Wiklund, Walter C. Willett, Ellen L. Goode, Jennifer B. Permuth, Harvey A. Risch, Brett M. Reid, Stephane Bezieau, Hermann Brenner, Andrew T. Chan, Jenny Chang-Claude, Thomas J. Hudson, Jonathan K. Kocarnik, Polly A. Newcomb, Robert E. Schoen, Martha L. Slattery, Emily White, Muriel A. Adank, Habibul Ahsan, Kristiina Aittomäki, Laura Baglietto, Carl Blomquist, Federico Canzian, Kamila Czene, Isabel dos-Santos-Silva, A. Heather Eliassen, Jonine D. Figueroa, Dieter Flesch-Janys, Olivia Fletcher, Montserrat Garcia-Closas, Mia M. Gaudet, Nichola Johnson, Per Hall, Aditi Hazra, Rebecca Hein, Albert Hofman, John L. Hopper, Astrid Irwanto, Mattias Johansson, Rudolf Kaaks, Muhammad G. Kibriya, Peter Lichtner, Jianjun Liu, Eiliv Lund, Enes Makalic, Alfons Meindl, Bertram Müller-Myhsok, Taru A. Muranen, Heli Nevanlinna, Petra H. Peeters, Julian Peto, Ross L. Prentice, Nazneen Rahman, Maria Jose Sanchez, Daniel F. Schmidt, Rita K. Schmutzler, Melissa C. Southey, Rulla Tamimi, Ruth C. Travis, Clare Turnbull, Andre G. Uitterlinden, Zhaoming Wang, Alice S. Whittemore, Xiaohong R. Yang, Wei Zheng, Daniel D. Buchanan, Graham Casey, David V. Conti, Christopher K. Edlund, Steven Gallinger, Robert W. Haile, Mark Jenkins, Loïc Le Marchand, Li Li, Noralene M. Lindor, Stephanie L. Schmit, Stephen N. Thibodeau, Michael O. Woods, Thorunn Rafnar, Julius Gudmundsson, Simon N. Stacey, Kari Stefansson, Patrick Sulem, Y. Ann Chen, Jonathan P. Tyrer, David C. Christiani, Yongyue Wei, Hongbing Shen, Zhibin Hu, Xiao-Ou Shu, Kouya Shiraishi, Atsushi Takahashi, Yohan Bossé, Ma'en Obeidat, David Nickle, Wim Timens, Matthew L. Freedman, Qiyuan Li, Daniela Seminara, Stephen J. Chanock, Jian Gong, Ulrike Peters, Stephen B. Gruber, Christopher I. Amos, Thomas A. Sellers, Douglas F. Easton, David J. Hunter, Christopher A. Haiman, Brian E. Henderson, Rayjean J. Hung
Journal: Cancer Research (2016)

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.