Mayo Clinic - AuthorCitation

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

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

Cancer Research | April 21, 2016 | Volume: 76 | Issue: 17 | Pages: 5103-5114

10.1158/0008-5472.can-15-2980 | PMID 27197191

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.