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

G. Fehringer, P. Kraft, Paul D. P. Pharoah, Rosalind A. Eeles, N. Chatterjee, Fredrick R. Schumacher, Joellen M. Schildkraut, S. Lindstrom, P. Brennan, H. Bickeboller, Richard S. Houlston, M.T. Landi, N. Caporaso, A. Risch, A. A. Al Olama, Sonja I Berndt, E.L. Giovannucci, H. Gronberg, Zsofia Kote-Jarai, Jun MaK. Muir, M. J. Stampfer, V.L. Stevens, Fredrik Wiklund, W.C. Willett, Ellen L. Goode, J. B. Permuth, Harvey A. Risch, B. M. Reid, S. Bezieau, H. Brenner, T.A. Chan, J. Chang-Claude, T.J. Hudson, J. K. Kocarnik, Polly A. Newcomb, R.E. Schoen, M. L. Slattery, E. White, M. A. Adank, H. Ahsan, K. Aittomaki, L. Baglietto, C. Blomquist, F. Canzian, K. Czene, I. dos Santos Silva, A. H. Eliassen, J.D. Figueroa, D. Flesch-Janys, O. Fletcher, M. Garcia-Closas, M. Gaudet, N. Johnson, P. Hall, A. Hazra, R. Hein, A. Hofman, John L. Hopper, A. Irwanto, M. Johansson, R. Kaaks, M.G. Kibriya, P. Lichtner, J. Liu, E. Lund, E. Makalic, A. Meindl, B. Muller-Myhsok, Taru A. Muranen, H. Nevanlinna, Petra H. Peeters, J. Peto, R. L. Prentice, N. Rahman, Anthony M. J. Sanchez, Daniel F. Schmidt, Rita K. Schmutzler, Melissa C. Southey, R. Tamimi, R.C. Travis, C. Turnbull, A. G. Uitterlinden, M. -Z. Wang, Alice S. Whittemore, X. H. R. Yang, W. Zheng, D. D. Buchanan, G. Casey, David V. Conti, Christopher K. Edlund, S. Gallinger, R. W. Haile, M. Jenkins, L. Le Marchand, L. Li, N.M. Lindor, S. L. Schmit, S. N. Thibodeau, M. O. Woods, T. Rafnar, J. Gudmundsson, S.N. Stacey, K. Stefansson, P. Sulem, A.Y. Chen, Jonathan P Tyrer, David C. Christiani, Y. Wei, H. B. Shen, Z. B. Hu, X.O. Shu, K. Shiraishi, A. Takahashi, Y. Bosse, M. Obeidat, D. Nickle, W. Timens, Matthew L. Freedman, Y.Q. Li, D. Seminara, Stephen J Chanock, J. Gong, U. Peters, Stephen B. Gruber, Christopher I. Amos, Thomas A. Sellers, Douglas F. Easton, David J. Hunter, Christopher A. Haiman, B.E. Henderson, Rayjean J. Hung, Ocac [Unknown], Practical Consortium, Res Hereditary Breast Ovarian Canc, Transdisciplinary Colorectal, Canc African Amer Breast, Canc African Ancestry Prostate

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Abstract

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 atCDKN2B-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. (C) 2016 AACR.
Original languageEnglish
Pages (from-to)5103-5114
Number of pages12
JournalCancer Research
Volume76
DOIs
Publication statusPublished - 2016

Cite this

Fehringer, G., Kraft, P., Pharoah, P. D. P., Eeles, R. A., Chatterjee, N., Schumacher, F. R., ... African Ancestry Prostate, C. (2016). Cross-Cancer Genome-Wide Analysis of Lung, Ovary, Breast, Prostate, and Colorectal Cancer Reveals Novel Pleiotropic Associations: Cancer Research. Cancer Research, 76, 5103-5114. https://doi.org/10.1158/0008-5472.can-15-2980