Background: Although genome-wide association studies (GWAS) have identified variants in approximately 40 susceptibility loci for colorectal cancer (CRC), there are few studies on the interactions between identified single-nucleotide polymorphisms (SNPs) and lifestyle risk factors. We evaluated whether smoking could modify associations between these genetic variants and CRC risk.
Methods: A total of 703 CRC patients and 1406 healthy controls were included in this case-control study from the National Cancer Center in Korea. Thirty CRC susceptibility SNPs identified in previous GWAS were genotyped. A logistic regression model was used to examine associations between the SNPs and smoking behaviors by sex. The interaction was estimated by including an additional interaction term in the model.
Results: In men, an increased CRC risk was observed for longer durations (OR>28 vs. ≤28years = 1.49 (95% CI = 1.11-1.98)), greater quantities (OR≥20 vs. <20cigarettes/day = 2.12 (1.61-2.79)), and longer pack-years of smoking (OR≥21 vs. <21pack-years = 1.78 (1.35-2.35)). In women, longer pack-years of smoking significantly increased CRC risk (OR≥5 vs. <5pack-years = 6.11 (1.10-34.00)). Moreover, there were significant interactions between smoking status and the polymorphisms rs1957636 at 14q22.3 (P interaction = 5.5 × 10-4) and rs4813802 at 20p12.3 (P interaction = 0.04) in men. Interactions between smoking status and the rs6687758 at 1q41 (P interaction = 0.03), duration and the rs174537 at 11q12.2 (P interaction = 0.05), and pack-years and the rs4813802 (P interaction = 0.04) were also found in women.
Conclusions: Associations between susceptibility SNPs and CRC risk may be modified by smoking behaviors, supporting the existence of gene-smoking interactions.
Keywords: Case-control study; Colorectal cancer; Gene-environment interaction; Single-nucleotide polymorphism; Smoking behaviors.