CYP2D6, CYP2E1 Gene Polymorphisms and Gastrointestinal Cancer Risk in Rural Maharashtra: A Hospital Based Case-Control Study.

Background: Cytochrome P450 (CYP) is a family phase I metabolizing enzymes important in xenobiotics metabolism. Genetic polymorphisms of CYPs have been comprehensively studied for their association with a range of diseases including cancer risk. In this study we assessed single nucleotide polymorphism (SNP) CYP2D6 and CYP2E1 genes and their role in gastrointestinal (GI) cancer susceptibility in the rural population of Maharashtra.

Methods: Genotyping of CYP2D6*4, CYP2E1*5B, CYP2E1*6, CYP2E1*7B genes among 200 GI cancer cases and equal number of controls was studied by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The Odds ratio (OR) with 95% confidence interval and p-value were evaluated to get the level of association of polymorphisms with risk of GI cancer, where p ≤0.005 was considered as statistically significant.

Results: After the analysis of CYP2D6 and CYP2E1 gene polymorphisms, we noticed that CYP2D6*4 (rs3892097) with heterozygous genotype (G/C) showed negative association with GI cancer risk (OR=0.43, 95% CI: 0.25-0.74; p=0.002) and CYP2E1*6 (rs6413432) variant genotype showed positive association (OR=2.85, 95% CI: 1.40-5.81; p=0.003) showed positive association with GI cancer risk in studied population.

Conclusion: The findings obtained from this study concluded that the polymorphic CYP2D6 was negatively associated; however CYP2E1*6 polymorphism was significantly associated with GI cancer risk in studied population.