Copy number polymorphism of glutathione-S-transferase genes (GSTM1 & GSTT1) in susceptibility to lung cancer in a high-risk population from north-east India

BACKGROUND & OBJECTIVES: Genetic polymorphisms in glutathione-S-transferase genes (GSTM1 and GSTT1) have been studied intensively for their potential role in lung cancer susceptibility. However, most of the studies on association between the polymorphisms and lung cancer do not distinguish between genotypes with one or two copies of the genes. The present study investigates the gene dosage effects of GSTT1 and GSTM1 copy number and their environmental interactions to examine the association of lung cancer risk with trimodular genotypes of the GSTs in a high-risk population from north-east India. METHODS: A total of 154 lung cancer cases and 154 age and sex matched controls from the high risk region of north-east India were analyzed by multiplex real-time PCR to determine the trimodal genotypes (+/+, +/- and -/-) in both the genes (GSTM1 and GSTT1). RESULTS: No significant association and gene dosage effect of GSTM1 gene copy number with lung cancer risk (P(trend)=0.13) were found. However, absence of GSTT1 conferred 68 per cent (OR=0.32;95%CI=0.15-0.71; P=0.005) reduced risk compared to the two copy number of the gene. There was evidence of gene dosage effect of GSTT1 gene (P(trend)=0.006). Tobacco smoking was a major environmental risk factor to lung cancer (OR=3.03;95%CI=1.73-5.31; P<0.001). However, its interaction with null genotype of GSTT1 conferred significant reduced risk to lung cancer (OR=0.30;95%CI=0.10-0.91; P=0.03). Further in only tobacco smokers, null genotype was associated with increased reduced risk [0.03(0.001-0.78)0.03; P(trend)=0.006]. No effect modification of GSTM1 was observed with lung cancer risk by environmental risk factors. INTERPRETATION & CONCLUSIONS: The results suggest that absence of GSTT1 null genotype may be associated with a reduced risk of lung cancer and the effect remains unchanged after interaction with smoking.