TY - JOUR
T1 - Cross-cancer genome-wide analysis of lung, ovary, breast, prostate, and colorectal cancer reveals novel pleiotropic associations
AU - Colorectal Transdisciplinary (CORECT) Study
AU - Ovarian Cancer Association Consortium (OCAC)
AU - The PRACTICAL Consortium
AU - Hereditary Breast and Ovarian Cancer Research Group Netherlands (HEBON)
AU - African American Breast Cancer Consortium (AABC)
AU - African Ancestry Prostate Cancer Consortium (AAPC)
AU - Fehringer, Gordon
AU - Kraft, Peter
AU - Pharoah, Paul D.
AU - Eeles, Rosalind A.
AU - Chatterjee, Nilanjan
AU - Schumacher, Fredrick R.
AU - Schildkraut, Joellen M.
AU - Lindström, Sara
AU - Brennan, Paul
AU - Bickeböller, Heike
AU - Houlston, Richard S.
AU - Landi, Maria Teresa
AU - Caporaso, Neil
AU - Risch, Angela
AU - Al Olama, Ali Amin
AU - Berndt, Sonja I.
AU - Giovannucci, Edward L.
AU - Grönberg, Henrik
AU - Kote-Jarai, Zsofia
AU - Ma, Jing
AU - Muir, Kenneth
AU - Stampfer, Meir J.
AU - Stevens, Victoria L.
AU - Wiklund, Fredrik
AU - Willett, Walter C.
AU - Goode, Ellen L.
AU - Permuth, Jennifer B.
AU - Risch, Harvey A.
AU - Reid, Brett M.
AU - Bezieau, Stephane
AU - Brenner, Hermann
AU - Chan, Andrew T.
AU - Chang-Claude, Jenny
AU - Hudson, Thomas J.
AU - Kocarnik, Jonathan K.
AU - Newcomb, Polly A.
AU - Schoen, Robert E.
AU - Slattery, Martha L.
AU - White, Emily
AU - Adank, Muriel A.
AU - Ahsan, Habibul
AU - Aittomäki, Kristiina
AU - Baglietto, Laura
AU - Blomquist, Carl
AU - Canzian, Federico
AU - Czene, Kamila
AU - Dos-Santos-silva, Isabel
AU - Eliassen, A. Heather
AU - Lindor, Noralene M.
AU - Thibodeau, Stephen N.
N1 - Publisher Copyright:
© 2016 American Association for Cancer Research.
PY - 2016/9/1
Y1 - 2016/9/1
N2 - 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 CDKN2BAS1 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 cancerassociated loci, identifying common mechanisms of cancer development and progression.
AB - 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 CDKN2BAS1 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 cancerassociated loci, identifying common mechanisms of cancer development and progression.
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U2 - 10.1158/0008-5472.CAN-15-2980
DO - 10.1158/0008-5472.CAN-15-2980
M3 - Article
C2 - 27197191
AN - SCOPUS:84986888945
SN - 0008-5472
VL - 76
SP - 5103
EP - 5114
JO - Cancer research
JF - Cancer research
IS - 17
ER -