Effects of interactions between common genetic variants and alcohol consumption on colorectal cancer risk
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Nan Song1, Aesun Shin1,2,3,*, Jae Hwan Oh4 and Jeongseon Kim3,*
1Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea
2Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Korea
3Molecular Epidemiology Branch, National Cancer Center, Goyang, Korea
4Center for Colorectal Cancer, National Cancer Center, Goyang, Korea
*These authors have contributed equally to this work
Aesun Shin, email: [email protected]
Jeongseon Kim, email: [email protected]
Keywords: colorectal cancer; gene and environment interaction; single-nucleotide polymorphism; alcohol consumption; case-control study
Received: June 01, 2017 Accepted: December 28, 2017 Published: January 06, 2018
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; ptrend<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.
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