Genetic variants in CYP and GST genes, smoking and risk for head and neck cancers: A gene-environment interaction hospital-based case-control study among Canadian Caucasians

The evidence for genetic polymorphisms in genes encoding cytochrome P450 (CYP) and glutathione S-transferase (GST) enzymes as risk factors for squamous cell carcinomas of the head and neck (SCCHN) in Caucasians is conflicting. Furthermore, the interactive effects with smoking have not been documented. We estimated the effects of five single nucleotide polymorphisms and two copy number variants associated with CYP and GST genes, as well as their interactive effects with smoking, on SCCHN risk among Caucasians from a case-control study conducted in Montreal, Canada. The study involved 389 incident SCCHN cases and 429 controls, frequency-matched by age and sex, recruited from four main hospitals between 2005 and 2013. Life-course-based interviews collected information on tobacco smoking history and other risk behaviors. DNA was isolated from oral exfoliated cells and genotyped for genetic variants. Unconditional logistic regression models estimated odds ratios (OR) and 95% confidence intervals (CI) for main, joint effect, stratum-specific and interaction estimates among non-, moderate and heavy smokers. Carriers of GSTP1 105Val (versus non-carriers) had a lower risk of SCCHN (OR = 0.71, 95% CI: 0.53, 0.95), which was observed for heavy smokers (OR = 0.59, 95% CI: 0.36, 0.95) and non-smokers alike (OR = 0.49, 95% CI: 0.24, 0.98). The decreased risk associations were also conserved among human papillomavirus negative individuals. There was no evidence for statistical interaction with smoking on additive or multiplicative scales for any of the variants analyzed. Of CYP and GST polymorphisms detected in Canadian Caucasians, only GSTP1 105Val was associated with a decreased risk for SCCHN.