Androgen-receptor gene CAG repeats, plasma testosterone levels, and risk of hepatitis B-related hepatocellular carcinoma

Ming Whei Yu*, Shu Wen Cheng, Ming Wei Lin, Shi Yi Yang, Yun Fan Liaw, Hung Chuen Chang, Tun Jen Hsiao, Shi Ming Lin, Shou Dong Lee, Pei Jer Chen, Chun Jen Liu, Chien Jen Chen

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

132 Scopus citations

Abstract

Background: 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. Methods: 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. Results: 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 four-fold increase in HCC risk compared with those with more than 24 repeats and testosterone levels in the lowest tertile. Conclusions: 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.

Original languageEnglish
Pages (from-to)2023-2028
Number of pages6
JournalJournal of the National Cancer Institute
Volume92
Issue number24
DOIs
StatePublished - 20 Dec 2000

Fingerprint

Dive into the research topics of 'Androgen-receptor gene CAG repeats, plasma testosterone levels, and risk of hepatitis B-related hepatocellular carcinoma'. Together they form a unique fingerprint.

Cite this