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.

Type

Journal

Cancer Research

Publisher

American Association for Cancer Research

Publication Date

09/2016

Volume

76

Pages

5103 - 5114

Addresses

Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital, Toronto, Canada.

Keywords

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)