Plasma Testosterone, SRD5A2 Genetic Polymorphism and Risk of Hepatocellular Carcinoma among Men with Chronic Hepatitis B CAG-Repeat Length in the Androgen Receptor Gene and Female Hepatocellular Carcinoma

• Main Authors: Yu-Ching Yang, 楊幼菁
• Other Authors: Chien-Jen Chen
• Format: Others
• Language: zh-TW
• Published: 2000
• Online Access: http://ndltd.ncl.edu.tw/handle/48774830180515489638

碩士 === 國立臺灣大學 === 流行病學研究所 === 88 === Abstract Objective：The specific aims of this study were:1) to assess the risk of hepatocellular carcinoma (HCC) associated with plasma testosterone level and the V89L polymorphism in steroid 5α-reductase type 2 (SRD5A2) gene among HBsAg-positive men in a nested case-control study;and 2) to investigate the association between a microsatellite( (CAG)n) within exon 1 of the androgen receptor(AR) gene and HCC in women by use of case-control study. Methods：A total of 110 incident cases of HCC and 110 matched controls identified from a cohort of 4841 male HBsAg carriers were tested for plasma testosterone level and SRD5A2 V89L genetic polymorphism. AR-CAG-repeat length was determined for 103 women with HCC and 183 healthy women .Genotyping was performed using polymerase chain reaction based methods on peripheral white blood cells or buccal cells. Results：Compared with male HBsAg carriers having LL genotype of the V89L polymorphism at SRD5A2, the multivariate-adjusted odds ratio (OR) of HCC for those who had VL and VV genotype was 2.0 (95% confident interval [CI]：1.0-4.0) and 3.5 (95% CI:1.4-8.6), respectively. The multivariate-adjusted ORs of HCC for male HBsAg carriers in increasing tertiles of plasma testosterone were 1.0, 1.4 (95%CI:0.6-3.3) and 3.1 (95%CI:1.4-6.8). Based on additive model, there was a synergistic interaction between the number of carrying the V allele of the V89L polymorphism and elevated testosterone levels in HCC risk. Compared with male HBsAg carriers in the lowest tertile of plasma testosterone who carried the LL genotype, the highest multivariate-adjusted OR was observed among those with both VV genotype and a testosterone level in the highest tertile (OR:7.6;95%CI:1.5-37.9).The association of HCC risk with plasma testosterone level and SRD5A2 was more striking among male HBsAg carriers who were relatively thin (body mass index≦22.9)、were younger(＜50 years)、had no smoking /drinking habit or had no history of hepatobiliary diseases .Long CAG-repeat sequence (＞22 repeats) in both AR alleles was significantly associated with increased risk of HCC in women (multivariate-adjusted OR: 2.6;95%CI: 1.0-6.5). Significantly increased risk associated with the AR genotype was observed only among female HBsAg carriers. There was no significant interaction of AR genotype with age at menarche/menopause、parity or a history of abortions in HCC risk. Conclusion：These results suggested that male HBsAg carriers who had increased plasma testosterone levels or at least one V allele of the V89L polymorphism in SRD5A2 were at increased risk of HCC. Longer AR-CAG repeats may play a role in the development of HCC among women.