Cytochrome P450 17 (CYP17), CYP2C19*2, CYP2C19*3 Gene Polymorphisms and Gastrointestinal Cancer Risk in Rural Maharashtra: A Hospital based Case-Control Study.

BACKGROUND

Gastrointestinal cancer (GI) is one of the most common cancer worldwide rapidly increasing in India too. Cytochrome P450 (CYP) family comprise a group of phase I metabolizing enzymes which are important in xenobiotics and carcinogen metabolism. Several studies revealed the association of metabolic genes with risk of cancers, but the results were ambiguous to support the evidences in case of GI cancer risk. These differences in earlier studies directed us to review the association of polymorphisms of metabolic genes including CYP17 and CYP2C19 (CYP2C192, CYP2C193) with GI cancer susceptibility in rural population of Maharashtra.

METHODS

Genetic polymorphism of CYP17 and CYP2C19 (CYP2C192, CYP2C193) genes among two hundred histologically confirmed gastrointestinal cancer cases and equal number of age and sex matched 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 ≤0.05 was considered as statistically significant.

RESULTS

After the regression analysis the results of genetic polymorphisms of CYP17 and CYP2C19 showed significant deviation from Hardy-Weinberg equilibrium for variant genotype of CYP2C192 (rs4244285) (OR=3.37 95% CI: 1.74-6.53; p=0.0003) which indicated functional association of CYP2C192 with GI cancer risk in the studied population. Similarly when we studied the association of CYP2C19*3 and CYP17 polymorphism, the variant genotypes did not show association with development of GI cancer among rural population of south-western Maharashtra.

CONCLUSION

The findings obtained from this study signified evident association of rs4244285 SNP of CYP2C19*2 with GI cancer risk in the studied rural population.