Glutathione S-transferase M1 and T1 null genotypes as risk factors for oral leukoplakia in ethnic Indian betel quid/tobacco chewers

Oral cancer is the most common cancer in males and third most common in fem ales in India, the main causative agent being the use of chewing tobacco wi th or without betel quid (BQ), However, nothing is known about the role of the host metabolic genes in oral cancer in ethnic Indian population. In thi s study, the prevalence of GSTM1 and GSTT1 null genotypes (GSTM1*2 and GSTT 1*2) in oral premalignant leukoplakia cases and controls was ascertained in genomic DNA by a multiplex PCR technique. Biopsies taken from 98 oral leuk oplakia patients and exfoliated cells from 82 healthy controls both of Indi an ethnicity were analysed, GSTM1*1 (active) was present in 83% and GSTT1*1 (active) was present in 78% of all control subjects, while prevalence of G STM1'*2 and GSTT1*2 null genotypes was significantly higher among oral leuk oplakia cases. The prevalence of GSTM1*2 in leukoplakia cases was 81.6% com pared with 17% in controls [odds ratio (OR), 22; 95% confidence interval (C I), 10-47] and GSTT1*2 was 75.5% in the cases versus 22% in controls (OR, 1 1; 95% CI, 5-22), Combined null genotypes of GSTM1 and GSTT1 prevailed in 6 0.2% of the cases with none detected in controls. Glutathione S-transferase M1 and T1 enzymes are both known to catalyse detoxification of reactive ox ygen species, lipid peroxidation products and tobacco-derived carcinogens t hat have been found in the saliva of BQ/tobacco chewers. Our results, still requiring confirmation by a larger study, demonstrate that the null genoty pes of both GSTM1 and GSTT1 increase with high penetrance, separately or in combination, the risk for developing leukoplakia in an Indian ethnic popul ation.