Genome-Wide Interaction Analyses between Genetic Variants and Alcohol Consumption and Smoking for Risk of Colorectal Cancer

CCFR and GECCO

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Genome-wide association studies (GWAS) have identified many genetic susceptibility loci for colorectal cancer (CRC). However, variants in these loci explain only a small proportion of familial aggregation, and there are likely additional variants that are associated with CRC susceptibility. Genome-wide studies of gene-environment interactions may identify variants that are not detected in GWAS of marginal gene effects. To study this, we conducted a genome-wide analysis for interaction between genetic variants and alcohol consumption and cigarette smoking using data from the Colon Cancer Family Registry (CCFR) and the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO). Interactions were tested using logistic regression. We identified interaction between CRC risk and alcohol consumption and variants in the 9q22.32/HIATL1 (Pinteraction = 1.76×10−8; permuted p-value 3.51x10-8) region. Compared to non-/occasional drinking light to moderate alcohol consumption was associated with a lower risk of colorectal cancer among individuals with rs9409565 CT genotype (OR, 0.82 [95% CI, 0.74–0.91]; P = 2.1×10−4) and TT genotypes (OR,0.62 [95% CI, 0.51–0.75]; P = 1.3×10−6) but not associated among those with the CC genotype (p = 0.059). No genome-wide statistically significant interactions were observed for smoking. If replicated our suggestive finding of a genome-wide significant interaction between genetic variants and alcohol consumption might contribute to understanding colorectal cancer etiology and identifying subpopulations with differential susceptibility to the effect of alcohol on CRC risk.

Original languageEnglish (US)
Article numbere1006296
JournalPLoS Genetics
Volume12
Issue number10
DOIs
StatePublished - Oct 1 2016

Fingerprint

smoking
colorectal neoplasms
Alcohol Drinking
alcohol
Colorectal Neoplasms
cancer
genome
Smoking
Genome
genotype
Genome-Wide Association Study
Genotype
gene
etiology
Gene-Environment Interaction
epidemiology
Genetic Loci
drinking
Molecular Epidemiology
subpopulation

ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics
  • Molecular Biology
  • Genetics
  • Genetics(clinical)
  • Cancer Research

Cite this

Genome-Wide Interaction Analyses between Genetic Variants and Alcohol Consumption and Smoking for Risk of Colorectal Cancer. / CCFR and GECCO.

In: PLoS Genetics, Vol. 12, No. 10, e1006296, 01.10.2016.

Research output: Contribution to journalArticle

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title = "Genome-Wide Interaction Analyses between Genetic Variants and Alcohol Consumption and Smoking for Risk of Colorectal Cancer",
abstract = "Genome-wide association studies (GWAS) have identified many genetic susceptibility loci for colorectal cancer (CRC). However, variants in these loci explain only a small proportion of familial aggregation, and there are likely additional variants that are associated with CRC susceptibility. Genome-wide studies of gene-environment interactions may identify variants that are not detected in GWAS of marginal gene effects. To study this, we conducted a genome-wide analysis for interaction between genetic variants and alcohol consumption and cigarette smoking using data from the Colon Cancer Family Registry (CCFR) and the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO). Interactions were tested using logistic regression. We identified interaction between CRC risk and alcohol consumption and variants in the 9q22.32/HIATL1 (Pinteraction = 1.76×10−8; permuted p-value 3.51x10-8) region. Compared to non-/occasional drinking light to moderate alcohol consumption was associated with a lower risk of colorectal cancer among individuals with rs9409565 CT genotype (OR, 0.82 [95{\%} CI, 0.74–0.91]; P = 2.1×10−4) and TT genotypes (OR,0.62 [95{\%} CI, 0.51–0.75]; P = 1.3×10−6) but not associated among those with the CC genotype (p = 0.059). No genome-wide statistically significant interactions were observed for smoking. If replicated our suggestive finding of a genome-wide significant interaction between genetic variants and alcohol consumption might contribute to understanding colorectal cancer etiology and identifying subpopulations with differential susceptibility to the effect of alcohol on CRC risk.",
author = "{CCFR and GECCO} and Jian Gong and Hutter, {Carolyn M.} and Newcomb, {Polly A.} and Ulrich, {Cornelia M.} and Bien, {Stephanie A.} and Campbell, {Peter T.} and Baron, {John A.} and Berndt, {Sonja I.} and Stephane Bezieau and Hermann Brenner and Graham Casey and Chan, {Andrew T.} and Jenny Chang-Claude and Mengmeng Du and David Duggan and Figueiredo, {Jane C.} and Steven Gallinger and Giovannucci, {Edward L.} and Haile, {Robert W.} and Harrison, {Tabitha A.} and Hayes, {Richard B.} and Michael Hoffmeister and Hopper, {John L.} and Hudson, {Thomas J.} and Jihyoun Jeon and Jenkins, {Mark A.} and Jonathan Kocarnik and S{\'e}bastien K{\"u}ry and {Le Marchand}, Loic and Yi Lin and Lindor, {Noralane Morey} and Reiko Nishihara and Shuji Ogino and Potter, {John D.} and Anja Rudolph and Schoen, {Robert E.} and Petra Schrotz-King and Daniela Seminara and Slattery, {Martha L.} and Thibodeau, {Stephen N} and Mark Thornquist and Reka Toth and Robert Wallace and Emily White and Shuo Jiao and Mathieu Lemire and Li Hsu and Ulrike Peters",
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AU - Newcomb, Polly A.

AU - Ulrich, Cornelia M.

AU - Bien, Stephanie A.

AU - Campbell, Peter T.

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AU - Gallinger, Steven

AU - Giovannucci, Edward L.

AU - Haile, Robert W.

AU - Harrison, Tabitha A.

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AU - Hsu, Li

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AB - Genome-wide association studies (GWAS) have identified many genetic susceptibility loci for colorectal cancer (CRC). However, variants in these loci explain only a small proportion of familial aggregation, and there are likely additional variants that are associated with CRC susceptibility. Genome-wide studies of gene-environment interactions may identify variants that are not detected in GWAS of marginal gene effects. To study this, we conducted a genome-wide analysis for interaction between genetic variants and alcohol consumption and cigarette smoking using data from the Colon Cancer Family Registry (CCFR) and the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO). Interactions were tested using logistic regression. We identified interaction between CRC risk and alcohol consumption and variants in the 9q22.32/HIATL1 (Pinteraction = 1.76×10−8; permuted p-value 3.51x10-8) region. Compared to non-/occasional drinking light to moderate alcohol consumption was associated with a lower risk of colorectal cancer among individuals with rs9409565 CT genotype (OR, 0.82 [95% CI, 0.74–0.91]; P = 2.1×10−4) and TT genotypes (OR,0.62 [95% CI, 0.51–0.75]; P = 1.3×10−6) but not associated among those with the CC genotype (p = 0.059). No genome-wide statistically significant interactions were observed for smoking. If replicated our suggestive finding of a genome-wide significant interaction between genetic variants and alcohol consumption might contribute to understanding colorectal cancer etiology and identifying subpopulations with differential susceptibility to the effect of alcohol on CRC risk.

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