Effects of interactions between common genetic variants and smoking on colorectal cancer

Abstract

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.