雄激素受体基因CAG重复序列、血浆睾酮水平与乙型肝炎相关肝细胞癌风险

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

作者信息

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

机构信息

Graduate Institute of Epidemiology, College of Public Health, National Taiwan University, Taipei.

出版信息

J Natl Cancer Inst. 2000 Dec 20;92(24):2023-8. doi: 10.1093/jnci/92.24.2023.

DOI:10.1093/jnci/92.24.2023

PMID:11121465

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 fourfold 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.

摘要

背景

在全球范围内，肝细胞癌（HCC）在男性中比在女性中更为普遍，这表明性激素和/或X染色体连锁基因可能参与肝癌发生过程。我们调查了台湾男性中雄激素受体（AR）基因（位于X染色体上）的三核苷酸（CAG）重复序列（称为“AR - CAG重复序列”）、血浆睾酮水平与HCC风险之间的关联。慢性乙型肝炎病毒（HBV）感染与HCC风险相关，在台湾地区呈高度流行。

方法

我们比较了285例患有HCC的HBV携带者和349例未患HCC的HBV携带者的AR - CAG重复序列数量。我们还对一项队列研究的参与者进行了巢式病例对照研究。前瞻性地收集了110例病例患者和239例对照受试者的血液，用于确定AR - CAG重复序列数量和血浆睾酮水平。所有统计检验均为双侧检验。

结果

与AR - CAG重复序列超过24次的HBV携带者相比，AR - CAG重复序列为20次或更少的HBV携带者发生HCC的总体比值比（OR）为1.72（95%置信区间[CI]=1.03 - 2.89）。这种关联仅在迟发性HCC患者中观察到（OR = 2.37；95%CI = 1.28 - 4.38）。在巢式病例对照研究中，与睾酮水平处于最低三分位数的HBV携带者相比，睾酮水平处于最高三分位数的HBV携带者发生HCC的风险在统计学上显著增加（OR = 2.06；95%CI = 1.14 - 3.70）。与迟发性疾病相比，睾酮水平升高与早发性疾病的关联更强（OR = 4.67；95%CI = 1.41 - 15.38）。与AR - CAG重复序列超过24次且睾酮水平处于最低三分位数的HBV携带者相比，AR - CAG重复序列为20次或更少且睾酮水平较高的HBV携带者发生HCC的风险增加了四倍。