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

Sarita Agrawal,Shraddha Singh,Abhjeet Chandra,Abbas Ali Mahdi,Amit Kumar Madeshiya,Devendra Singh,Shipra Dwivedi

doi:10.7314/apjcp.2015.16.13.5557

Abstract

Cholelithiasis is associated in 54%-98% of patients with carcinoma of the gallbladder, and a high incidence 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 with altered serum levels of estrogens. Thus, we investigated whether the CYP-17 MspA1 gene polymorphism might impact on risk of gall bladder cancers or gallstones, as well as to determine if this gene polymorphism might be linked with estrogen serum levels and lipid profile among the North Indian gall bladder cancer or gallstone patients. CYP-17 gene polymorphisms (MspA1) were genotyped with PCR-RFLP in cancer patients (n=96), stone patients (n=102), cancer+stone patients (n=52) and age/sex matched control subjects (n=256). Lipid profile was estimated using a commercial kit and serum estrogen was measured using ELISA. The majority of the patients in all groups were females. The lipid profile and estrogen level were significantly higher among the study as compared to control groups. The frequency of mutant allele A2 of CYP17 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) when compared with the control group. However there was no significant association between genotypes of CYP17 MspA1 gene polymorphism and circulating serum level of estrogen and lipid profile. A higher frequency of mutant genotype A1A2 as well as mutant allele A2 of CYP-17 gene polymorphism is significantly associated with risk of gallbladder cancer and stones. Elevated levels of estrogen and an altered lipid profile can be used as predictors ofgall bladder stones and cancer in post menopausal females in India.

Highlights

Gall bladder cancer (GBC) is a rare neoplasm with varying demographic distribution in different parts of the world and it is common in the population of Chile, Japan, Peru and Korea (Curado et al, 2007)
The comparison between stone and cancer + stone group shows that the level of total cholesterol (TC), TG, Low density lipoprotein (LDL), Very low density lipoprotein (VLDL), estrogen was significantly (p=0.0001) higher and High density lipoprotein (HDL) was significantly lower among cancer+stone group
The comparison of cancer, stone and cancer+stone with the control group shows that the level of TC, TG, LDL, VLDL, estrogen was significantly higher and HDL was significantly lower among the all study groups. (Table 1)

Summary

Introduction

Gall bladder cancer (GBC) is a rare neoplasm with varying demographic distribution in different parts of the world and it is common in the population of Chile, Japan, Peru and Korea (Curado et al, 2007). We investigated whether the CYP-17 MspA1 gene polymorphism might impact on risk of gall bladder cancers or gallstones, as well as to determine if this gene polymorphism might be linked with estrogen serum levels and lipid profile among the North Indian gall bladder cancer or gallstone patients. The frequency of mutant allele A2 of CYP17 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) when compared with the control group. There was no significant association between genotypes of CYP17 MspA1 gene polymorphism and circulating serum level of estrogen and lipid profile. Conclusions: A higher frequency of mutant genotype A1A2 as well as mutant allele A2 of CYP-17 gene polymorphism is significantly associated with risk of gallbladder cancer and stones.

Methods

Results

Conclusion