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

• Published in: Cancer research (Chicago, Ill.) Vol. 76; no. 17; pp. 5103 - 5114
• Main Authors: Fehringer, Gordon, Kraft, Peter, Pharoah, Paul D, 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, Risch, Angela, Amin Al Olama, Ali, Berndt, Sonja I, Giovannucci, Edward L, Grönberg, Henrik, Kote-Jarai, Zsofia, Ma, Jing, Muir, Kenneth, Stampfer, Meir J, Stevens, Victoria L, Wiklund, Fredrik, Willett, Walter C, Goode, Ellen L, Permuth, Jennifer B, Risch, Harvey A, Reid, Brett M, Bezieau, Stephane, Brenner, Hermann, Chan, Andrew T, Chang-Claude, Jenny, Hudson, Thomas J, Kocarnik, Jonathan K, Newcomb, Polly A, Schoen, Robert E, Slattery, Martha L, White, Emily, Adank, Muriel A, Ahsan, Habibul, Aittomäki, Kristiina, Baglietto, Laura, Blomquist, Carl, Canzian, Federico, Czene, Kamila, Dos-Santos-Silva, Isabel, Eliassen, A Heather, Figueroa, Jonine D, Flesch-Janys, Dieter, Fletcher, Olivia, Garcia-Closas, Montserrat, Gaudet, Mia M, Johnson, Nichola, Hall, Per, Hazra, Aditi, Hein, Rebecca, Hofman, Albert, Hopper, John L, Irwanto, Astrid, Johansson, Mattias, Kaaks, Rudolf, Kibriya, Muhammad G, Lichtner, Peter, Liu, Jianjun, Lund, Eiliv, Makalic, Enes, Meindl, Alfons, Müller-Myhsok, Bertram, Muranen, Taru A, Nevanlinna, Heli, Peeters, Petra H, Peto, Julian, Prentice, Ross L, Rahman, Nazneen, Sanchez, Maria Jose, Schmidt, Daniel F, Schmutzler, Rita K, Southey, Melissa C, Tamimi, Rulla, Travis, Ruth C, Turnbull, Clare, Uitterlinden, Andre 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, Le Marchand, Loïc, Li, Li, Lindor, Noralene M, Schmit, Stephanie L, Thibodeau, Stephen N, Woods, Michael O
• Format: Journal Article
• Language: English
• Published: United States 01.09.2016
• Subjects: Breast Neoplasms - genetics; Colorectal Neoplasms - genetics; Female; Genome-Wide Association Study; Genotype; Humans; Lung Neoplasms - genetics; Male; Medicin och hälsovetenskap; Ovarian Neoplasms - genetics; Prostatic Neoplasms - genetics
• ISSN: 0008-5472; 1538-7445; 1538-7445
• DOI: 10.1158/0008-5472.can-15-2980

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.