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Genotype-environment interactions in microsatellite stable/microsatellite instability-low colorectal cancer: results from a genome-wide association study.

Authors :
Figueiredo JC
Lewinger JP
Song C
Campbell PT
Conti DV
Edlund CK
Duggan DJ
Rangrej J
Lemire M
Hudson T
Zanke B
Cotterchio M
Gallinger S
Jenkins M
Hopper J
Haile R
Newcomb P
Potter J
Baron JA
Le Marchand L
Casey G
Source :
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology [Cancer Epidemiol Biomarkers Prev] 2011 May; Vol. 20 (5), pp. 758-66. Date of Electronic Publication: 2011 Feb 25.
Publication Year :
2011

Abstract

Background: Genome-wide association studies (GWAS) have led to the identification of a number of common susceptibility loci for colorectal cancer (CRC); however, none of these GWAS have considered gene-environment (G × E) interactions. Therefore, it is unclear whether current hits are modified by environmental exposures or whether there are additional hits whose effects are dependent on environmental exposures.<br />Methods: We conducted a systematic search for G × E interactions using genome wide data from the Colon Cancer Family Registry that included 1,191 cases of microsatellite stable (MSS) or microsatellite instability-low (MSI-L) CRC and 999 controls genotyped using either the Illumina Human1M or Human1M-Duo BeadChip. We tested for interactions between genotypes and 14 environmental factors using 3 methods: a traditional case-control test, a case-only test, and the recently proposed 2-step method by Murcray and colleagues. All potentially significant findings were replicated in the ARCTIC Study.<br />Results: No G × E interactions were identified that reached genome-wide significance by any of the 3 methods. When analyzing previously reported susceptibility loci, 7 significant G × E interactions were found at a 5% significance level. We investigated these 7 interactions in an independent sample and none of the interactions were replicated.<br />Conclusions: Identifying G × E interactions will present challenges in a GWAS setting. Our power calculations illustrate the need for larger sample sizes; however, as CRC is a heterogeneous disease, a tradeoff between increasing sample size and heterogeneity needs to be considered.<br />Impact: The results from this first genome-wide analysis of G × E in CRC identify several challenges, which may be addressed by large consortium efforts.<br /> (©2011 AACR.)

Details

Language :
English
ISSN :
1538-7755
Volume :
20
Issue :
5
Database :
MEDLINE
Journal :
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
Publication Type :
Academic Journal
Accession number :
21357381
Full Text :
https://doi.org/10.1158/1055-9965.EPI-10-0675