The Relationship Between Polymorphisms In Estrogen-metabolizing Genes CYP17, COMT And Risk Of Cirrhosis Or Hepatocellular Carcinoma In Hepatitis B Infected Patients

Objective:To test the hypothesis whether genetic polymorphisms in estrogenetabolizing genes CYP17 and COMT,impact on the risk of cirrhosis or hepatocellular carcinoma in hepatitis B infected patients of Shandong province.Methods:1.According to the definition of The Blue Print of Prevention and Cure of Virosis Hepatitis-2000,The study included 404 HBV patients:99 hepatocelluar carcinomas(HCC),117 cirrhosis,87 hepatitis and 96 HBsAg carriers.85 healthy individuals were used to assess allele frequency in the general population.2.TheT/C polymorphism in the 5'untranslated region(-34)bp of the CYP17 gene and Val 158 Met polymorphism of COMT caused by the missense mutation of G 158 A in exon 4 were detected by polymerase chainreaction-restriction fragment length polymorphism(PCR-RFLP),And HBV was detected by means of ELISA.3.The results were analysisted by SPSS 13.0.Genotype frequencis among patient categories were compared by x~2 test.Odds ratios(ORs)and 95% confidence intervals(95%CI)were calculated using carriers as reference category. Multivariable logistic regression was used to model independent associationsand to perform age and sex adjustments,P＜0.05 were significantly.Hardy-Weinberg analysis was performed to assess deviation of genotype distribution from what expected according to allele frequencies both in control subjects and cases and it was found to be consistent with equilibrium.Results:1.Of the 85 control subjects,we obtained that Allele frequent cies of CYP17 A1/A1,A1/A2 and A2/A2 were 20.0%,47.5%and32.5%,COMT Val/Val,Val/Met and Met/Met were 39.0%,48.1%and 13.0%,which were to accord with Hardy-Weinberg.2.Compared to control subjects,there was not a significant difference in the distribution of CYP17 A1/A1,A1/A2,A2/A2 and COMT Val/ Val,Val/Met,Met/Met genotypes frequency in the HBV-infected patients.3.In chronic active hepatitis B patients,CYP17(-34)A2/A2 geno-types frequency was significantly higher than in HBV carriers:29.3%:15.4%,OR of A2/A2 genotypes is 2.28,P:0.03.But it became no statistically significant in males or females.There was not a significant difference in the distribution of A1/A1 genotype.4.Compared to HBV carriers,ORs for hepatic cirrhosis patients were 1.68 (95%CI:0.81～3.46,P＞0.05)in A2/A2 patients compared with other genotypes. There was not a significant difference in the distribution of A2/A2 genotype of males,females or post-menopausal women,so was A1/A1 and A1/A2 genotypes.5.Differences were more evident comparing carriers and HCC patients,with a twofold risk of HCC for the(-34)A2/A2 patients(OR:2.38;95%CI:1.16～4.88;P:0.02).Females mostly contributed to this association(OR:5.93,P:0.002)and OR values increased in post menopausal women(OR:6.18,P:0.003),but not in male subjects.In female HCC cases,frequency of A1/A2 genetype was significantly lower than in carriers group(5.5%:60.8%),P:0.04.6.The frequency distribution of the COMT alleles was analysed by groups,but did not show any significant difference between patients and controls or among patient categories.7.We found a strong independent risk factor of HCC and cirrhosis represented by cigarette smoking(OR:19.03;95%CI:1.29-27.9;P:0.03)of HBV infected women, in addition to age and CYP17 A2/A2 genotype.Conclusion: 1.Our data did not show significant differences between carriers and cirrhosis. CYP17(-34)A2/A2 genetype might be not associated with cirrhosis risk in HBV-infected patients.2.Compared to carriers,the(-34)A2/A2 genotype of CYP17 significantly elevated risk of HCC patients.The results suggested that CYP17 MspAlI genotypes A2/A2 may be related to liver cancer risk in HBV-infected women. A1/A2 genetype might be resistant to HCC in HBV-infected women.3.COMT gene polymorphisms,might not affect the expresion of hepatitis B virus related liver disease.4.Cigarette smoking may be a strong independent risk factor of cirrhosis and HCC in HBV-infected women.