Genetic polymorphism of the CYP1A1, CYP2E1, GSTM1 and GSTT1 genes and lung cancer susceptibility in a north indian population.

CYP1A1, CYP2E1, GSTM1 and GSTT1 polymorphisms were evaluated in north Indian lung cancer patients and controls. The estimated relative risk for lung cancer associated with the CYP1A1*2C allele was 2.68. Apart from the CYP1A1*2C genotype, there was no attributable risk in relation to other genotypes when analyzed singly. However, in the presence of a single copy of the variant CYP1A1 (CYP1A1*1/2A) and null GSTT1 genes, there was a three-fold increased risk for lung cancer; when stratified histologically the relative risk increased to 3.7 in case of SQCC. Similarly individuals carrying the mutant CYP1A1*2C genotype and single copy of the variant CYP1A1 Mspl allele, had a relative risk of 2.85 for lung cancer. In case of the GSTM1 and CYP1A1 genotypes, null GSTM1 and variant Msp1 alleles had two-fold elevated risk for SQCC. On the other hand CYP1A1*2C and null GSTM1 genotype had a 3.5-fold elevated risk for SCLC. Stratified analysis indicated a multiplicative interaction between tobacco smoking and variant CYP1A1 genotypes on the risk for SQCC and SCLC. The heavy smokers (BI > 400) with CYP1A1*2C genotype were at a very high risk to develop SCLC with an OR of 29.30 (95% CI = 2.42-355, p = 0.008). Taken together, these findings, the first to be analyzed in north Indian population, suggest that combined GSTT1 , GSTM1 and CYP1A1 polymorphisms could be susceptible to lung cancer induced by bidi (an Indian cigarette) smoking.