RT Journal Article
SR Electronic
T1 Pleiotropic effects of genetic risk variants for other cancers on colorectal cancer risk: PAGE, GECCO and CCFR consortia
JF Gut
JO Gut
FD BMJ Publishing Group Ltd and British Society of Gastroenterology
SP 800
OP 807
DO 10.1136/gutjnl-2013-305189
VO 63
IS 5
A1 Iona Cheng
A1 Jonathan M Kocarnik
A1 Logan Dumitrescu
A1 Noralane M Lindor
A1 Jenny Chang-Claude
A1 Christy L Avery
A1 Christian P Caberto
A1 Shelly-Ann Love
A1 Martha L Slattery
A1 Andrew T Chan
A1 John A Baron
A1 Lucia A Hindorff
A1 Sungshim Lani Park
A1 Fredrick R Schumacher
A1 Michael Hoffmeister
A1 Peter Kraft
A1 Anne M Butler
A1 David J Duggan
A1 Lifang Hou
A1 Chris S Carlson
A1 Kristine R Monroe
A1 Yi Lin
A1 Cara L Carty
A1 Sue Mann
A1 Jing Ma
A1 Edward L Giovannucci
A1 Charles S Fuchs
A1 Polly A Newcomb
A1 Mark A Jenkins
A1 John L Hopper
A1 Robert W Haile
A1 David V Conti
A1 Peter T Campbell
A1 John D Potter
A1 Bette J Caan
A1 Robert E Schoen
A1 Richard B Hayes
A1 Stephen J Chanock
A1 Sonja I Berndt
A1 Sebastien Küry
A1 Stephane Bézieau
A1 Jose Luis Ambite
A1 Gowri Kumaraguruparan
A1 Danielle M Richardson
A1 Robert J Goodloe
A1 Holli H Dilks
A1 Paxton Baker
A1 Brent W Zanke
A1 Mathieu Lemire
A1 Steven Gallinger
A1 Li Hsu
A1 Shuo Jiao
A1 Tabitha A Harrison
A1 Daniela Seminara
A1 Christopher A Haiman
A1 Charles Kooperberg
A1 Lynne R Wilkens
A1 Carolyn M Hutter
A1 Emily White
A1 Dana C Crawford
A1 Gerardo Heiss
A1 Thomas J Hudson
A1 Hermann Brenner
A1 William S Bush
A1 Graham Casey
A1 Loïc Le Marchand
A1 Ulrike Peters
YR 2014
UL http://gut.bmj.com/content/63/5/800.abstract
AB Objective Genome-wide association studies have identified a large number of single nucleotide polymorphisms (SNPs) associated with a wide array of cancer sites. Several of these variants demonstrate associations with multiple cancers, suggesting pleiotropic effects and shared biological mechanisms across some cancers. We hypothesised that SNPs previously associated with other cancers may additionally be associated with colorectal cancer. In a large-scale study, we examined 171 SNPs previously associated with 18 different cancers for their associations with colorectal cancer. Design We examined 13 338 colorectal cancer cases and 40 967 controls from three consortia: Population Architecture using Genomics and Epidemiology (PAGE), Genetic Epidemiology of Colorectal Cancer (GECCO), and the Colon Cancer Family Registry (CCFR). Study-specific logistic regression results, adjusted for age, sex, principal components of genetic ancestry, and/or study specific factors (as relevant) were combined using fixed-effect meta-analyses to evaluate the association between each SNP and colorectal cancer risk. A Bonferroni-corrected p value of 2.92×10−4 was used to determine statistical significance of the associations. Results Two correlated SNPs—rs10090154 and rs4242382—in Region 1 of chromosome 8q24, a prostate cancer susceptibility region, demonstrated statistically significant associations with colorectal cancer risk. The most significant association was observed with rs4242382 (meta-analysis OR=1.12; 95% CI 1.07 to 1.18; p=1.74×10−5), which also demonstrated similar associations across racial/ethnic populations and anatomical sub-sites. Conclusions This is the first study to clearly demonstrate Region 1 of chromosome 8q24 as a susceptibility locus for colorectal cancer; thus, adding colorectal cancer to the list of cancer sites linked to this particular multicancer risk region at 8q24.