Microsomal Epoxide Hydrolase Polymorphisms And Haplotypes As Determinants Of Hepatitis B Virusand He-winflash

Arts-and-Entertainment Hepatocellular carcinoma (HCC) is one of the most .mon malignant tumor worldwide, representing the fifth most .mon cancer, while being the third leading cause of death due to cancer. It shows an annual incidence of over 600,000.1 The incidence of HCC is the highest in Asia, followed by Africa, Europe, and North and South America. It varies among ethnic groups, and in the last two decades, increasing trends in the incidence of HCC have been noted in Australia, Central Europe, UK, Japan, and North America.2 In the US alone, overall age-adjusted incidence rates of HCC tripled between 1975 and 2005, rising from 1.6 per 100,000 to 4.9 per 100,000.3,4 Hepatocellular carcinoma occurs more often in men than in women and is usually seen in people of age 50 or older. However, the age varies in different parts of the world. Background Hepatocellular carcinoma (HCC) is the fifth most .mon cancer and third leading cause of death worldwide. Main causes of HCC are hepatitis B virus (HBV) and hepatitis C virus (HCV) infections. mEPHX, a xenobiotic metabolizing enzyme, exhibits a dual role of procarcinogen detoxification and activation, hence considered as a cancer risk factor as well as a protective factor. Two known polymorphic forms of mEPHX, exon in exon 3 and 4, are associated with the development of HCC. Objective To determine the association of genotypes and haplotypes of mEPHX with risk of HCC developments separately in HBV- and HCV-infected carriers and patients with hepatitis. Methods Polymerase chain reactions (PCR) were carried out using primers to amplify exon 3 (113 Tyr?His variant) and exon 4 (139 His?Arg) polymorphic sites. To distinguish the wild and variant forms, PCR amplification products were digested with restriction endonucleases EcoRV and Rsa1 for exons 3 and 4, respectively. Result Exon 3 genotypes, Y113H and H113H, shared a protective association with HBV-chronic hepatitis infection (P < 0.001 and P< 0.01, respectively) as well as HBV-HCC development (P < 0.001) among HBV-carrier group, while Y113H acts as a risk factor for HCV-chronic hepatitis development (P < 0.001) as well as for HCC development (P < 0.01) with HCV-carrier group as reference. Both H139R and R139R, exon 4 genotypes, acted as a risk factor for HBV/HCV-chronic hepatitis infection and for HBV/HCV-HCC development (P ranges from < 0.05 to < 0.001) with HBV/HCV carriers as reference. 113His-139His and 113His-139Arg haplotypes shared a significant negative and positive association, respectively, with HBV hepatitis and HBV-HCC risk. 113Tyr-139Arg haplotype acted as a risk for HCV-HCC development. Conclusion Polymorphic and haplotypic variant forms of mEPHX exon 3 and 4 variably determine the susceptibility to develop HCC in HBV- and HCV-carrier subjects. About the Author: 相关的主题文章: