Effects of interactions between common genetic variants and alcohol consumption on colorectal cancer risk

Nan Song; Aesun Shin; Jae Hwan Oh; Jeongseon Kim

doi:10.18632/oncotarget.23997

Effects of interactions between common genetic variants and alcohol consumption on colorectal cancer risk

Oncotarget. 2018 Jan 6;9(5):6391-6401. doi: 10.18632/oncotarget.23997. eCollection 2018 Jan 19.

Authors

Nan Song¹, Aesun Shin^{1

2

3}, Jae Hwan Oh⁴, Jeongseon Kim³

Affiliations

¹ Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
² Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Korea.
³ Molecular Epidemiology Branch, National Cancer Center, Goyang, Korea.
⁴ Center for Colorectal Cancer, National Cancer Center, Goyang, Korea.

Abstract

Background: Genome-wide association studies (GWAS) have identified approximately 40 common genetic loci associated with colorectal cancer risk. To investigate possible gene-environment interactions (GEIs) between GWAS-identified single-nucleotide polymorphisms (SNPs) and alcohol consumption with respect to colorectal cancer, a hospital-based case-control study was conducted.

Results: Higher levels of alcohol consumption as calculated based on a standardized definition of a drink (1 drink=12.5g of ethanol) were associated with increased risk of colorectal cancer (OR=2.47, 95% CI=1.62-3.76 for heavy drinkers [>50g/day] compared to never drinkers; p_trend<0.01). SNP rs6687758 near the DUSP10 gene at 1q41 had a statistically significant interaction with alcohol consumption in analyses of standardized drinks (p=4.6×10^-3), although this did not surpass the corrected threshold for multiple testing. When stratified by alcohol consumption levels, in an additive model the risk of colorectal cancer associated with the G allele of rs6687758 tended to increase among individuals in the heavier alcohol consumption strata. A statistically significant association between rs6687758 and colorectal cancer risk was observed among moderate alcohol drinkers who consumed between >12.5 and ≤50g of alcohol per day (OR=1.46, 95% CI=1.01-2.11).

Methods: A total of 2,109 subjects (703 colorectal cancer patients and 1,406 healthy controls) were recruited from the Korean National Cancer Center. For genotyping, 30 GWAS-identified SNPs were selected. A logistic regression model was used to evaluate associations of SNPs and alcohol consumption with colorectal cancer risk. We also tested GEIs between SNPs and alcohol consumption using a logistic model with multiplicative interaction terms.

Conclusions: Our results suggest that SNP rs6687758 at 1q41 may interact with alcohol consumption in the etiology of colorectal cancer.

Keywords: alcohol consumption; case-control study; colorectal cancer; gene and environment interaction; single-nucleotide polymorphism.