GSTM1, GSTT1, GSTP1, CYP1A1, and NAT1 polymorphisms, tobacco use, and the risk of head and neck cancer

Squamous cell carcinoma of the head and neck (SCCHN), including the oral ca vity, pharynx, and larynx, provides an ideal tumor model to investigate gen e-environment interaction. We conducted a hospital-based case-control study including 182 cases with newly diagnosed SCCHN and 202 controls with nonne oplastic conditions of the head and neck that required surgery. Lifetime to bacco use and risk of SCCHN were evaluated in relation to the Polymorphisms Of GSTM1, GSTT1, GSTP1, CYP1A1, and NAT1. The main effects of genotype wer e associated with a slightly increased risk of SCCHN for GSTP1 [age-, race- , and sex-adjusted odds ratio (OR), 1.2; confidence interval (CI), 0.8-1.9] , GSTT1 (OR, 1.2; CI, 0.7-2.3), and NAT1 (OR, 1.1; CI, 0.7-1.7), The joint effects of genotype combinations showed some excess risk for the combinatio n of the GSTM1 null genotype and the CYP1A1 IIe/Val polymorphism (OR, 2.6; CI, 0.7-10.3). The analysis of the joint effects (interaction) of the "at-r isk" genotypes and tobacco use did not reveal any interaction on either the multiplicative or additive scale for GSTM1, GSTP1, or CYP1A1, However, the re was a suggestion of an interaction on the additive scale between the pac k-years of tobacco use and the GSTT1 null genotype. The combined heterozygo te and homozygote NAT1*10 genotypes also had a suggestive interaction with tobacco smoking history. The results of this study suggest a possible gene- environment interaction for certain carcinogen metabolizing enzymes, but la rger studies that fully evaluate the interaction are needed.