Combined Effect of Smoking and Polymorphisms in Tobacco Carcinogen-Metabolizing Enzymes CYP1A1 and GSTM1 on the Head and Neck Cancer Risk in North Indians

摘要

Tobacco consumption contributes to the etiology of majority of cancers, and polymorphisms in tobacco-metabolizing enzymes may modulate susceptibility to head and neck cancer (HNC). The aim of this study was to determine whether genetic polymorphisms in genes CYP1A1 and GSTM1, involved in metabolism of major classes of tobacco-derived carcinogens, may predispose to development of HNC in a North Indian population. In this case-control study, 203 HNC patients and 201 control subjects were genotyped for four variants of CYP1A1 using polymerase chain reaction-restriction fragment length polymorphism, and GSTM1 was analyzed for copy number variations by real-time polymerase chain reaction. Haplotype analysis was performed for the CYP1A1 gene using PHASE version 2.1. CYP1A1 CC (T3801C) (odds ratio [OR], 3.49; 95% confidence interval [CI], 1.34-9.05), GSTM1 single copy (OR, 2.63; 95% CI, 1.54-4.51), and null genotypes (OR, 4.37; 95% CI, 2.61-7.29) were found to be significantly associated with an increased risk of HNC. The gene-environment interactions revealed significant interactions among smokers carrying CYP1A1 AG (A2455G) and GSTM1 copy number variants. CYP1A1 haplotypes carrying variant 3801C allele, C-A-C (OR, 2.45; 95% CI, 1.56-3.83), and C-G-C (OR, 2.39; 95% CI, 1.35-4.25) were found to be associated with a twofold increased risk of HNC. GSTM1 copy number variations and CYP1A1 polymorphisms individually as well in interaction with tobacco consumption may increase the risk of HNC.