Association of Cytochrome-17 (MspA1) Gene Polymorphism with Risk of Gall Bladder Stones and Cancer in North India

Background: Cholelithiasis is associated in 54%-98% of patients with carcinoma of the gallbladder, and a highincidence among females suggests a role of female hormones in the etiology of the disease. Cytochrome P450C17α(CYP-17) is a key enzyme involved in estrogen metabolism and polymorphisms in CYP-17 are associated withaltered serum levels of estrogens. Thus, we investigated whether the CYP-17 MspA1 gene polymorphism mightimpact on risk of gall bladder cancers or gallstones, as well as to determine if this gene polymorphism mightbe linked with estrogen serum levels and lipid profile among the North Indian gall bladder cancer or gallstonepatients. Materials and
Methods: CYP-17 gene polymorphisms (MspA1) were genotyped with PCR-RFLPin cancer patients (n=96), stone patients (n=102), cancer + stone patients (n=52) and age/sex matched controlsubjects (n= 256). Lipid profile was estimated using a commercial kit and serum estrogen was measured usingELISA.
Results: The majority of the patients in all groups were females. The lipid profile and estrogen levelwere significantly higher among the study as compared to control groups. The frequency of mutant allele A2 ofCYP17 MspA1 gene polymorphism was higher among cancer (OR=5.13, 95% CI+3.10-8.51, p=0.0001), stone(OR=5.69, 95%CI=3.46-9.37, p=0.0001) and cancer + stone (OR=3.54, 95%CI=1.90-6.60, p=0.0001) whencompared with the control group. However there was no significant association between genotypes of CYP17MspA1 gene polymorphism and circulating serum level of estrogen and lipid profile.
Conclusions: A higherfrequency of mutant genotype A1A2 as well as mutant allele A2 of CYP-17 gene polymorphism is significantlyassociated with risk of gallbladder cancer and stones. Elevated levels of estrogen and an altered lipid profile canbe used as predictors ofgall bladder stones and cancer in post menopausal females in India.