Cross-Cancer Genome-Wide Analysis of Lung, Ovary, Breast, Prostate, and Colorectal Cancer Reveals Novel Pleiotropic Associations.
;
A Heather
Eliassen
;
Jonine D
Figueroa
;
Dieter
Flesch-Janys
;
Olivia
Fletcher
;
Montserrat
Garcia-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
Liu
;
Eiliv
Lund
;
Enes
Makalic
;
Alfons
Meindl
;
Bertram
Müller-Myhsok
;
Taru A
Muranen
;
Heli
Nevanlinna
;
Petra H
Peeters
;
Julian
Peto
;
Ross L
Prentice
;
Nazneen
Rahman
;
Maria Jose
Sanchez
;
Daniel F
Schmidt
;
Rita K
Schmutzler
;
Melissa C
Southey
;
Rulla
Tamimi
;
Ruth C
Travis
;
Clare
Turnbull
;
Andre G
Uitterlinden
;
Zhaoming
Wang
;
Alice S
Whittemore
;
Xiaohong R
Yang
;
Wei
Zheng
;
Daniel D
Buchanan
;
Graham
Casey
;
David V
Conti
;
Christopher K
Edlund
;
Steven
Gallinger
;
Robert W
Haile
;
Mark
Jenkins
;
Loïc
Le Marchand
;
Li
Li
;
Noralene M
Lindor
;
Stephanie L
Schmit
;
Stephen N
Thibodeau
;
Michael O
Woods
;
Thorunn
Rafnar
;
Julius
Gudmundsson
;
Simon N
Stacey
;
Kari
Stefansson
;
Patrick
Sulem
;
Y Ann
Chen
;
Jonathan P
Tyrer
;
David C
Christiani
;
Yongyue
Wei
;
Hongbing
Shen
;
Zhibin
Hu
;
Xiao-Ou
Shu
;
Kouya
Shiraishi
;
Atsushi
Takahashi
;
Yohan
Bossé
;
Ma'en
Obeidat
;
David
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
;
Ovarian Cancer Association Consortium (OCAC)
;
PRACTICAL Consortium
;
Hereditary Breast and Ovarian Cancer Research Group Netherlands
;
Colorectal Transdisciplinary (CORECT) Study
;
African American Breast Cancer Consortium (AABC) and African Anc
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(2016)
Cross-Cancer Genome-Wide Analysis of Lung, Ovary, Breast, Prostate, and Colorectal Cancer Reveals Novel Pleiotropic Associations.
Cancer research, 76 (17).
pp. 5103-5114.
ISSN 0008-5472
DOI: 10.1158/0008-5472.CAN-15-2980
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.