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

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

Genome-wide association study

Breast cancer

Prostate cancer

2016

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 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.

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“Cross-Cancer Genome-Wide Analysis of Lung, Ovary, Breast, Prostate, and Colorectal Cancer Reveals Novel Pleiotropic Associations” is a paper by Gordon Fehringer Peter Kraft Paul D.P. Pharoah Rosalind Eeles Nilanjan Chatterjee Fredrick Schumacher Joellen M. Schildkraut Sara Lindström Paul Brennan Heike Bickeböller Richard S. Houlston Maria Teresa Landi Neil E. Caporaso Angela Risch Ali Amin Al Olama Sonja I. Berndt Edward Giovannucci Henrik Grönberg Zsofia Kote‐Jarai Jing Ma Kenneth Muir Meir J. Stampfer Victoria L. Stevens Fredrik Wiklund Walter C. Willett Ellen L. Goode Jennifer B. Permuth Harvey A. Risch Brett M. Reid Stéphane Bézieau Hermann Brenner Andrew T. Chan Jenny Chang‐Claude Thomas J. Hudson Jonathan K. Kocarnik Polly A. Newcomb Robert E. Schoen Martha L. Slattery Emily White Muriel A. Adank Habibul Ahsan Kristiina Aittomäki Laura Baglietto Carl Blomquist Federico Canzian Kamila Czene Isabel dos Santos Silva A. Heather Eliassen Jonine D. Figueroa Dieter Flesch‐Janys Olivia Fletcher Montserrat García-Closas Mia M. Gaudet Nichola Johnson Per Hall Aditi Hazra Rebecca Hein Albert Hofman John L. Hopper Astrid Irwanto Mattias Johansson Rudolf Kaaks Muhammad G. Kibriya Peter Lichtner Jianjun Li Eiliv Lund Enes Makalic Alfons Meindl Bertram Müller‐Myhsok Taru A. Muranen Heli Nevanlinna Petra H.M. Peeters Julian Peto Ross L. Prentice Nazneen Rahman María José Sánchez Daniel F. Schmidt Rita K. Schmutzler Melissa C. Southey Rulla M. Tamimi Ruth C. Travis Clare Turnbull André G. Uitterlinden Zhaoming Wang Alice S. Whittemore Xiaohong R. Yang Zheng Wang Daniel D. Buchanan Graham Casey David V. Conti Christopher K. Edlund Steven Gallinger Robert W. Haile Mark A. Jenkins Loı̈c Le Marchand Li Li Noralene M. Lindor Stephanie L. Schmit Stephen N. Thibodeau Michael O. Woods Thorunn Rafnar Jūlı́us Guðmundsson Simon Stacey Kári Stéfansson Patrick Sulem Yian Ann Chen Jonathan Tyrer David C. Christiani Yongyue Wei Hongbing Shen Zhibin Hu Xiao‐Ou Shu Kouya Shiraishi Atsushi Takahashi Yohan Bossé Ma’en Obeidat David C. Nickle Wim Timens Matthew L. Freedman Qiyuan Li Daniela Seminara Stephen J. Chanock Jian Gong Ulrike Peters Stephen B. Gruber Christopher I. Amos Thomas A. Sellers Douglas F. Easton David J. Hunter Christopher A. Haiman Brian E. Henderson Rayjean J. Hung published in 2016. It has an Open Access status of “bronze”. You can read and download a PDF Full Text of this paper here.