CYP2E1 polymorphisms and gene-environment interactions in the risk of upper aerodigestive tract cancers among Indians.

INTRODUCTION

The CYP2E1 enzyme is responsible for the metabolic activation of several procarcinogens into reactive metabolites that result in carcinogenesis. The genetic polymorphisms that modify these enzymatic activities may be associated with upper aerodigestive tract cancer risk.

METHODS

This hospital-based study evaluated CYP2E11B, CYP2E15B and CYP2E1*6 polymorphisms in 408 histopathologically confirmed cases and 220 population-based controls using PCR-RFLP methods.

RESULTS

The multivariate logistic regression analyses demonstrated no significant differences between groups for all three polymorphisms when analyzed separately. However, the gene-environment interactions analyses revealed significant interactions among tobacco smokers (11-20 pack years), 20-40 pack years and > 40 pack years), regular tobacco chewers and alcoholics carrying CYP2E11B mutant genotypes. Similarly, CYP2E16 polymorphisms resulted in significant interactions among tobacco smokers (> 40 pack years) and regular tobacco chewers on the multiplicative scale.

CONCLUSION

The significant gene-environment interactions observed for CYP2E11B and CYP2E16 polymorphic genotypes may confer a substantial risk for upper aerodigestive tract cancers among Indians.