PLoS Genetics (Oct 2016)

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

  • Jian Gong,
  • Carolyn M Hutter,
  • Polly A Newcomb,
  • Cornelia M Ulrich,
  • Stephanie A Bien,
  • Peter T Campbell,
  • John A Baron,
  • Sonja I Berndt,
  • Stephane Bezieau,
  • Hermann Brenner,
  • Graham Casey,
  • Andrew T Chan,
  • Jenny Chang-Claude,
  • Mengmeng Du,
  • David Duggan,
  • Jane C Figueiredo,
  • Steven Gallinger,
  • Edward L Giovannucci,
  • Robert W Haile,
  • Tabitha A Harrison,
  • Richard B Hayes,
  • Michael Hoffmeister,
  • John L Hopper,
  • Thomas J Hudson,
  • Jihyoun Jeon,
  • Mark A Jenkins,
  • Jonathan Kocarnik,
  • Sébastien Küry,
  • Loic Le Marchand,
  • Yi Lin,
  • Noralane M Lindor,
  • Reiko Nishihara,
  • Shuji Ogino,
  • John D Potter,
  • Anja Rudolph,
  • Robert E Schoen,
  • Petra Schrotz-King,
  • Daniela Seminara,
  • Martha L Slattery,
  • Stephen N Thibodeau,
  • Mark Thornquist,
  • Reka Toth,
  • Robert Wallace,
  • Emily White,
  • Shuo Jiao,
  • Mathieu Lemire,
  • Li Hsu,
  • Ulrike Peters,
  • CCFR and GECCO

DOI
https://doi.org/10.1371/journal.pgen.1006296
Journal volume & issue
Vol. 12, no. 10
p. e1006296

Abstract

Read online

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.