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.

Steven Gallinger | Peter Kraft | Nazneen Rahman | Paul Brennan | Julian Peto | Nilanjan Chatterjee | Kari Stefansson | David C Christiani | Mattias Johansson | Kamila Czene | Fredrik Wiklund | Yongyue Wei | Hongbing Shen | Alfons Meindl | Bertram Müller-Myhsok | Sara Lindström | Jian Gong | John L Hopper | Enes Makalic | Daniel F Schmidt | Jonine D Figueroa | Hermann Brenner | Maria Teresa Landi | David V Conti | Stephen B Gruber | Per Hall | Heli Nevanlinna | Christopher A Haiman | Kristiina Aittomäki | Brian E Henderson | Stephen J Chanock | Laura Baglietto | Olivia Fletcher | Nichola Johnson | Dieter Flesch-Janys | Wei Zheng | Jenny Chang-Claude | Henrik Grönberg | Jing Ma | Albert Hofman | Ellen L Goode | Montserrat Garcia-Closas | David J Hunter | Christopher I Amos | Clare Turnbull | Douglas F Easton | Eiliv Lund | A Heather Eliassen | Thomas J Hudson | Walter C Willett | Stephane Bezieau | Emily White | Ulrike Peters | Angela Risch | Graham Casey | Alice S Whittemore | Habibul Ahsan | Aditi Hazra | Atsushi Takahashi | Qiyuan Li | Melissa C Southey | Y Ann Chen | Richard S Houlston | Thomas A Sellers | Wim Timens | Federico Canzian | Li Li | Ross L Prentice | Stephanie L Schmit | Julius Gudmundsson | Thorunn Rafnar | Rebecca Hein | Sonja I Berndt | Andrew T Chan | Martha L Slattery | Michael O Woods | Heike Bickeböller | Joellen M Schildkraut | Robert W Haile | Rita K Schmutzler | Meir J Stampfer | Jianjun Liu | Astrid Irwanto | A. Whittemore | A. Hofman | A. Uitterlinden | M. Obeidat | Y. Bossé | W. Willett | K. Stefánsson | T. Hudson | T. Sellers | N. Rahman | Hongbing Shen | D. Nickle | K. Czene | P. Hall | H. Brenner | J. Chang-Claude | H. Grönberg | S. Chanock | M. García-Closas | E. Goode | D. Hunter | D. Seminara | S. Gruber | N. Chatterjee | M. Woods | R. Prentice | P. Sulem | R. Eeles | Z. Kote-Jarai | J. Hopper | B. Henderson | C. Haiman | S. Thibodeau | M. Southey | D. Easton | P. Kraft | R. Tamimi | Qiyuan Li | P. Pharoah | J. Peto | C. Amos | D. Conti | L. Le Marchand | M. Stampfer | Zhaoming Wang | R. Houlston | F. Schumacher | E. Giovannucci | F. Wiklund | Zhibin Hu | X. Shu | W. Zheng | D. Christiani | J. Gudmundsson | T. Rafnar | S. Stacey | S. Berndt | O. Fletcher | N. Johnson | H. Nevanlinna | Jianjun Liu | K. Muir | S. Lindström | P. Peeters | G. Casey | M. Freedman | M. Kibriya | H. Ahsan | S. Gallinger | C. Turnbull | T. Muranen | K. Aittomäki | A. Irwanto | M. Adank | R. Hein | A. Meindl | R. Schmutzler | B. Müller-Myhsok | P. Lichtner | E. Makalic | D. Schmidt | D. Flesch‐Janys | L. Baglietto | J. Figueroa | J. Tyrer | P. Newcomb | U. Peters | A. Risch | M. Jenkins | F. Canzian | H. Bickeböller | E. White | A. Takahashi | R. Schoen | M. Johansson | R. Kaaks | M. Slattery | V. Stevens | Jian Gong | H. Risch | R. Hung | J. Schildkraut | D. Buchanan | R. Haile | Jing Ma | Yongyue Wei | W. Timens | P. Brennan | M. Landi | C. Edlund | N. Caporaso | A. Hazra | E. Lund | R. Travis | K. Shiraishi | S. Bézieau | M. Gaudet | A. Eliassen | Xiaohong R. Yang | A. Amin Al Olama | G. Fehringer | Li Li | J. Permuth | M. Sanchez | Zhibin Hu | Zhaoming Wang | Patrick Sulem | Matthew L Freedman | Harvey A Risch | Edward L Giovannucci | Rudolf Kaaks | Daniela Seminara | Xiao-Ou Shu | Peter Lichtner | Neil Caporaso | Loïc Le Marchand | Stephen N Thibodeau | Fredrick R Schumacher | Rosalind A Eeles | Andre G Uitterlinden | Mark Jenkins | Paul D Pharoah | Kenneth Muir | Zsofia Kote-Jarai | Robert E Schoen | Muhammad G Kibriya | Polly A Newcomb | Ali Amin Al Olama | Jennifer B Permuth | Ruth C Travis | Victoria L Stevens | Mia M Gaudet | Simon N Stacey | Rayjean J Hung | Y. A. Chen | Petra H Peeters | Yohan Bossé | Kouya Shiraishi | Rulla Tamimi | D. Christiani | Isabel Dos-Santos-Silva | Jonathan P Tyrer | Stephanie L. Schmit | W. Willett | Taru A Muranen | Ma'en Obeidat | Brett M Reid | Gordon Fehringer | David Nickle | Xiaohong R Yang | Daniel D Buchanan | Muriel A Adank | Jonathan K Kocarnik | Carl Blomquist | Maria Jose Sanchez | Christopher K Edlund | Noralene M Lindor | Chris Amos | C. Blomquist | T. Hudson | J. Hopper | A. Chan | J. Gong | B. Reid | D. J. Hunter | M. Sánchez | N. Lindor | I. dos-Santos-Silva | S. Schmit | N. M. Lindor | Sonja I. Berndt | Chang-Claude Jenny | C. Haiman | Christopher A Haiman | A. Uitterlinden | P. Peeters | A. Hofman | P. Hall | M. Jenkins | Jing Ma | B. Henderson | D. Flesch-Janys | Ali Amin Al Olama

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