9 research outputs found
Genome-Wide Interaction Analyses between Genetic Variants and Alcohol Consumption and Smoking for Risk of Colorectal Cancer
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 pvalue
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