Cross-Cancer Genome-Wide Analysis of Lung, Ovary, Breast, Prostate, and Colorectal Cancer Reveals Novel Pleiotropic Associations.
; 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; 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; Colorectal Transdisciplinary (CORECT) Study; African American Breast Cancer Consortium (AABC) and African Anc and
(2016)
Cross-Cancer Genome-Wide Analysis of Lung, Ovary, Breast, Prostate, and Colorectal Cancer Reveals Novel Pleiotropic Associations.
Cancer research, 76 (17).
pp. 5103-5114.
ISSN 0008-5472
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.