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

نویسندگان

  • Gordon Fehringer
  • Peter Kraft
  • Paul D Pharoah
  • Rosalind A Eeles
  • Nilanjan Chatterjee
  • Fredrick R Schumacher
  • Joellen M Schildkraut
  • Sara Lindström
  • Paul Brennan
  • Heike Bickeböller
  • Richard S Houlston
  • Maria Teresa Landi
  • Neil Caporaso
  • Angela Risch
  • Ali Amin Al Olama
  • Sonja I Berndt
  • Edward L 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
  • Stephane Bezieau
  • 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 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
چکیده

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.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

A Cross-Cancer Genetic Association Analysis of the DNA Repair and DNA Damage Signaling Pathways for Lung, Ovary, Prostate, Breast, and Colorectal Cancer.

BACKGROUND DNA damage is an established mediator of carcinogenesis, although genome-wide association studies (GWAS) have identified few significant loci. This cross-cancer site, pooled analysis was performed to increase the power to detect common variants of DNA repair genes associated with cancer susceptibility. METHODS We conducted a cross-cancer analysis of 60,297 single nucleotide polymor...

متن کامل

Commentary: Two-sample Mendelian randomization: opportunities and challenges

A et al. Body mass index and lung cancer risk: results from the ICARE study, a large, population-based case-control study. A et al. Stress decreases the ability to resist smoking and potentiates smoking intensity and reward. Anthropometric factors and ovarian cancer risk: a systematic review and nonlinear dose-response meta-analysis of prospective studies. Association of oral contraceptive use,...

متن کامل

Genome-wide Meta-analyses of Breast, Ovarian and Prostate Cancer Association Studies Identify Multiple New Susceptibility Loci Shared by At Least Two Cancer Types

Breast, ovarian, and prostate cancers are hormone-related and may have a shared genetic basis but this has not been investigated systematically by genome-wide association (GWA) studies. Metaanalyses combining the largest GWA meta-analysis data sets for these cancers totaling 112,349 cases and 116,421 controls of European ancestry, all together and in pairs, identified at P < 10−8 seven new cros...

متن کامل

Circulating vitamin D concentration and risk of seven cancers: Mendelian randomisation study

Objective To determine if circulating concentrations of vitamin D are causally associated with risk of cancer.Design Mendelian randomisation study.Setting Large genetic epidemiology networks (the Genetic Associations and Mechanisms in Oncology (GAME-ON), the Genetic and Epidemiology of Colorectal Cancer Consortium (GECCO), and the Prostate Cancer Association Group to Investigate Cancer Associat...

متن کامل

Genetic Variation on 9p22 Is Associated with Abnormal Ovarian Ultrasound Results in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial

BACKGROUND A recent ovarian cancer genome-wide association study (GWAS) identified a locus on 9p22 associated with reduced ovarian cancer risk. The single nucleotide polymorphism (SNP) markers localize to the BNC2 gene, which has been associated with ovarian development. METHODS We analyzed the association of 9p22 SNPs with transvaginal ultrasound (TVU) screening results and CA-125 blood leve...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:
  • Cancer research

دوره 76 17  شماره 

صفحات  -

تاریخ انتشار 2016