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- Title
Androgen-receptor gene CAG repeats, plasma testosterone levels, and risk of hepatitis B-related hepatocellular carcinoma.
- Authors
Yu, M W; Cheng, S W; Lin, M W; Yang, S Y; Liaw, Y F; Chang, H C; Hsiao, T J; Lin, S M; Lee, S D; Chen, P J; Liu, C J; Chen, C J
- Abstract
<bold>Background: </bold>Worldwide, hepatocellular carcinoma (HCC) is more prevalent in men than in women, suggesting that sex hormones and/or X-chromosome-linked genes may be involved in hepatocarcinogenesis. We investigated the association of a trinucleotide (CAG) repeat in the androgen receptor (AR) gene (located on the X chromosome) termed "AR-CAG repeats," levels of plasma testosterone, and the risk of HCC in Taiwanese men. Chronic hepatitis B virus (HBV) infection, which is associated with risk of HCC, is hyperendemic in Taiwan.<bold>Methods: </bold>We compared the number of AR-CAG repeats in 285 HBV carriers with HCC and in 349 HBV carriers without HCC. We also conducted a nested case--control study on participants in a cohort study. Blood was collected prospectively from 110 case patients and 239 control subjects and was used to determine the number of AR-CAG repeats and plasma testosterone level. All statistical tests were two-sided.<bold>Results: </bold>The overall odds ratio (OR) for HCC was 1.72 (95% confidence interval [CI] = 1.03--2.89) for HBV carriers with 20 or fewer AR-CAG repeats compared with those with more than 24 repeats. This association was observed only in patients with late-onset HCC (OR = 2.37; 95% CI = 1.28--4.38). In the nested case-control study, HBV carriers in the highest tertile of testosterone levels had a statistically significantly increased risk of HCC (OR = 2.06; 95% CI = 1.14--3.70) compared with those in the lowest tertile. Elevated testosterone was more strongly associated with early-onset (OR = 4.67; 95% CI = 1.41--15.38) than late-onset disease. HBV carriers with 20 or fewer AR-CAG repeats and higher testosterone levels had a fourfold increase in HCC risk compared with those with more than 24 repeats and testosterone levels in the lowest tertile.<bold>Conclusions: </bold>Higher levels of androgen signaling, reflected by higher testosterone levels and 20 or fewer AR-CAG repeats, may be associated with an increased risk of HBV-related HCC in men.
- Subjects
PURINE metabolism; CELL receptors; COMPARATIVE studies; DNA; HEPATOCELLULAR carcinoma; HETEROCYCLIC compounds; LIVER tumors; LONGITUDINAL method; RESEARCH methodology; MEDICAL cooperation; RESEARCH; TESTOSTERONE; EVALUATION research; RELATIVE medical risk; CASE-control method; CHRONIC hepatitis B; ODDS ratio; DISEASE complications
- Publication
JNCI: Journal of the National Cancer Institute, 2000, Vol 92, Issue 24, p2023
- ISSN
0027-8874
- Publication type
journal article