Hormonal markers and hepatitis B virus-related hepatocellular carcinoma risk: a nested case-control study among men
Hormonal markers and hepatitis B virus-related hepatocellular carcinoma risk: a nested case-control study among men
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DOI：
10.1093/jnci/93.21.1644
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发表时间：
2001-11-07
期刊：
影响因子：
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通讯作者：
Chen, CJ
中科院分区：
文献类型：
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作者：
Yu, MW;Yang, YC;Chen, CJ
背景：男性中与B型肝炎病毒（HBV）相关的肝细胞癌（HCC）的发病率高于女性。我们研究了内源性性激素水平或肝硬化相关因素是否可能影响男性肝癌的风险。方法：从1988年至1992年，收集了4841名台湾男性HBV携带者的基线血液样本，这些携带者没有被诊断为肝癌。血浆睾酮、雌二醇水平与妊娠相关因子细胞色素P450 c17 α基因多态性（CYP 17，A1与A2等位基因），类固醇5 α-还原酶II型（SRD 5A 2，缬氨酸[V]与亮氨酸[L]等位基因）和雄激素受体对119例随访12年的HCC患者和238例对照者进行了CAG重复数（AR）检测。所有统计检验均为双侧检验。结果如下：肝细胞癌的风险随着睾酮浓度的增加而增加（优势比[OR]（最高）（相对于最低三分位数）2.97; 95%置信区间[CI] = 1.54至5.70; P-趋势< .001），且SRD 5A 2 V89 L多态性的V等位基因数量增加（ORVV（与LL，基因型）= 2.47; 95% CI = 1.21至5.03; P趋势= 0.011）AR基因CAG重复次数较少（< 23次重复）与HCC风险增加1.64倍（95% CI = 1.00至2.68）相关。虽然CYP 17基因型单独并不增加HCC的风险，但有证据表明基因-基因相互作用，因为CYP 17 A1等位基因在AR基因CAG重复较少的情况下统计学显著增加HCC的风险（OR = 2.51; 95%CI = 1.06至5.94）。我们发现SRD 5A 2 VV基因型和较少的AR基因CAG重复序列之间存在类似的相互作用（OR = 5.58; 95%CI = 1.86 - 16.71）。体重指数（BMI）改变了HCC与睾酮和SRD 5A 2基因型的相关性;在低BMI男性中，睾酮最高三分位数与最低三分位数以及SRD 5A 2 VV基因型与LL基因型的多变量校正OR为7.63（95%CI = 2.13至27.27）和8.64（95%CI = 2.75至27.14）。雌二醇或睾酮与雌二醇比值与HCC之间没有明显的相关性。结论：雄激素信号通路可能影响男性HBV相关HCC的风险。
Background: The incidence of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) is higher in men than in women. We examined whether endogenous sex hormone levels or hormone-related factors might affect the risk of HCC in men. Methods: Baseline blood samples were collected from 4841 male Taiwanese HBV carriers without diagnosed HCC from 1988 through 1992. Plasma testosterone and estradiol levels and genetic polymorphisms in the hormone-related factors cytochrome P450c17 alpha (CYP17, Al versus A2 alleles), steroid 5 alpha -reductase type II (SRD5A2, valine [V] versus leucine [L] alleles), and androgen receptor (AR, number of CAG repeats) were assayed among 119 case patients who were diagnosed with HCC during 12 years of follow-up and 238 control subjects. All statistical tests were two-sided. Results: The risk of HCC increased with increasing concentrations of testosterone (odds ratio [OR](highest) (versus lowest tertile) 2,97; 95% confidence interval [CI] = 1.54 to 5.70; P-trend < .001) and with increasing number of the V allele of the SRD5A2 V89L polymorphism (ORVV (versus LL, genotype) = 2.47; 95% CI = 1.21 to 5.03; P-trend = .011)Fewer AR gene CAG repeats (< 23 repeats) were associated with a 1.64-fold (95% CI = 1.00 to 2.68) increased risk of HCC. Although the CYP17 genotype alone did not increase the risk of HCC, there was evidence of a gene-gene interaction, because the CYP17 Al allele statistically significantly increased the risk of HCC in the presence of fewer AR gene CAG repeats (OR = 2.51; 95% CI = 1.06 to 5.94). We found a similar interaction between the SRD5A2 VV genotype and fewer AR gene CAG repeats (OR = 5.58; 95% CI = 1.86 to 16.71). Body mass index (BMI) modified the association of HCC with testosterone and SRD5A2 genotype; in men with low BMI, multivariate-adjusted ORs for the highest tertile of testosterone versus the lowest and the SRD5A2 VV genotype versus the LL genotype were 7.63 (95 % CI = 2.13 to 27.27) and 8.64 (95 % CI = 2.75 to 27.14), respectively. No clear associations were found between estradiol or testosterone-to-estradiol ratio and HCC. Conclusions: Pathways involving androgen signaling may affect the risk of HBV-related HCC among men.