\it{Human Glutathione S-transferase A1} Polymorphism and Susceptibility to Oral Squamous Cell Carcinoma in Japanese

ABSTRACT

Objectives: Glutathione S-transferase (GST) A1 catalyses the activated heterocyclic aromatic amine carcinogen N-acetoxy-2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (N-OAc-PhIP). This case-control study was carried out to examine whether the genetic polymorphism of GSTA1 is associated with the risk of oral squamous cell carcinoma among Japanese people in relation to their smoking status. Methods: In this study, 97 Japanese oral squamous cell carcinoma patients and 457 healthy controls were compared for the frequencies of the GSTA1 genotypes (*A -567T,-69C,-52G, *B -567G,-69T,-52A). Results: The frequencies of GSTA1 *A/*B+*B/*B genotypes were 32.3% in male cancer patients and 11.4% in female cancer patients, compared with 20.1% in the male control group (Odds ratio (OR)=1.86; 95% confidence interval (CI) 0.99-3.46) and 23.1% in the female control group (OR=0.58; 95% CI 0.18-1.81). The GSTA1 *A/*B+ *B/*B genotypes were associated with an 86% increased risk of oral squamous cell carcinoma among males, albeit without statistical significance. Also, among male smokers, the frequency of GSTA1 *A/*B+*B/*B genotypes was significantly higher among the oral squamous cell carcinoma patients (33.3%) than among the controls (19.6%). The OR of the male smokers with the GSTA1 *A/*B+ *B/*B genotypes for oral squamous cell carcinoma was 1.97 (95% CI 1.02-3.79). Conclusions: We present the first evidence of an association between GSTA1*B and oral squamous cell carcinoma among smokers. This study suggests that the GSTA1 polymorphism and tobacco smoke-derived PhIP are associated with oral squamous cell carcinoma susceptibility among male smokers.