Cross-Cancer Genome-Wide Analysis of Lung, Ovary, Breast, Prostate, and Colorectal Cancer Reveals Novel Pleiotropic Associations.
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.
Fehringer, G; Kraft, P; Pharoah, PD; Eeles, RA; Chatterjee, N; Schumacher, FR; Schildkraut, JM; Lindström, S; Brennan, P; Bickeböller, H; Houlston, RS; Landi, MT; Caporaso, N; Risch, A; Amin Al Olama, A; Berndt, SI; Giovannucci, EL; Grönberg, H; Kote-Jarai, Z; Ma, J; Muir, K; Stampfer, MJ; Stevens, VL; Wiklund, F; Willett, WC; Goode, EL; Permuth, JB; Risch, HA; Reid, BM; Bezieau, S; Brenner, H; Chan, AT; Chang-Claude, J; Hudson, TJ; Kocarnik, JK; Newcomb, PA; Schoen, RE; Slattery, ML; White, E; Adank, MA; Ahsan, H; Aittomäki, K; Baglietto, L; Blomquist, C; Canzian, F; Czene, K; Dos-Santos-Silva, I; Eliassen, AH; Figueroa, JD; Flesch-Janys, D; Fletcher, O; Garcia-Closas, M; Gaudet, MM; Johnson, N; Hall, P; Hazra, A; Hein, R; Hofman, A; Hopper, JL; Irwanto, A; Johansson, M; Kaaks, R; Kibriya, MG; Lichtner, P; Liu, J; Lund, E; Makalic, E; Meindl, A; Müller-Myhsok, B; Muranen, TA; Nevanlinna, H; Peeters, PH; Peto, J; Prentice, RL; Rahman, N; Sanchez, MJ; Schmidt, DF; Schmutzler, RK; Southey, MC; Tamimi, R; Travis, RC; Turnbull, C; Uitterlinden, AG; Wang, Z; Whittemore, AS; Yang, XR; Zheng, W; Buchanan, DD; Casey, G; Conti, DV; Edlund, CK; Gallinger, S; Haile, RW; Jenkins, M; Le Marchand, L; Li, L; Lindor, NM; Schmit, SL; Thibodeau, SN; Woods, MO; Rafnar, T; Gudmundsson, J; Stacey, SN; Stefansson, K; Sulem, P; Chen, YA; Tyrer, JP; Christiani, DC; Wei, Y; Shen, H; Hu, Z; Shu, X-O; Shiraishi, K; Takahashi, A; Bossé, Y; Obeidat, M; Nickle, D; Timens, W; Freedman, ML; Li, Q; Seminara, D; Chanock, SJ; Gong, J; Peters, U; Gruber, SB; Amos, CI; Sellers, TA; Easton, DF; Hunter, DJ; Haiman, CA; Henderson, BE; Hung, RJ; Ovarian Cancer Association Consortium (OCAC), ; PRACTICAL Consortium, ; Hereditary Breast and Ovarian Cancer Research Group Netherlands (HEBON), ; Colorectal Transdisciplinary (CORECT) Study, ; African American Breast Cancer Consortium (AABC) and African Ancestry Prostate Cancer Consortium (AAPC),
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