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

Abstract

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.