Association of testicular germ cell tumor with polymorphisms in estrogen receptor and steroid metabolism genes
Association of testicular germ cell tumor with polymorphisms in estrogen receptor and steroid metabolism genes
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DOI：
10.1677/erc-09-0176
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发表时间：
2010-03-01
影响因子：
3.9
通讯作者：
Foresta, Carlo
中科院分区：
文献类型：
--
作者：
Ferlin, Alberto;Ganz, Francesco;Foresta, Carlo
通常认为睾丸生殖细胞瘤（TGCT）的发生受内分泌控制。特别是，雄激素/雌激素水平和/或活性失衡被认为是TGCT发生和进展的关键事件。此外，最近的证据表明TGCT有很强的遗传成分。在这项研究中，我们分析了雌激素受体（ESR）基因和类固醇激素代谢基因的遗传变异是否与TGCT相关。我们对234例TGCT患者和218例对照者的11个基因的17个多态性标记进行了基因分型：（ESR 1和ESR 2）; CYP 19 A1（芳香酶）; 17 β-羟基类固醇脱氢酶1型和4型（HPD 17 B1和HPD 17 B4）将强效雄激素和雌激素转化为弱激素的脱氢酶;细胞色素P450羟化酶CYP 1A 1、CYP 1A 2和CYP 1B 1;以及代谢酶COMT、SULT 1A 1和SULT 1 E1。我们观察到HSD 17 B4中rs 11205与TGCT显著相关。在该位点上，每拷贝一个次要A等位基因，TGCT风险增加两倍（比值比（OR）= 2.273，95%置信区间（CI）= 1.737-2.973）。与携带主要G等位基因的纯合子相比，携带次要A等位基因的纯合子与TGCT的风险增加4倍以上（OR = 4.561，95%CI = 2.615-7.955）。恶性肿瘤（OR = 5.327，95%CI = 2.857-9.931）和非恶性肿瘤（OR = 3.222，95%CI = 1.471-7.059）的危险性均增加。本研究首次发现HSD 17 B4基因多态性与TGCT相关。我们的研究结果扩展了目前关于遗传贡献在睾丸癌易感性中的作用的知识，并支持激素代谢基因的变化可能改变睾丸癌发生中所涉及的激素环境的假设。内分泌相关癌症（2010）17 17-25
It is generally assumed that the development of testicular germ cell tumor (TGCT) is under endocrine control. In particular, unbalanced androgen/estrogen levels and/or activity are believed to represent the key events for TGCT development and progression. Furthermore, recent evidence has suggested a strong genetic component for TGCT. In this study, we analyzed whether a genetic variation in estrogen receptor (ESR) genes and steroid hormone metabolism genes is associated with TGCT. We genotyped for 17 polymorphic markers in 11 genes in 234 TGCT cases and 218 controls: ESR (ESR1 and ESR2); CYP19A1 (aromatase); 17 beta-hydroxysteroid dehydrogenase types 1 and 4 (HSD17B1 and HSD17B4) dehydrogenases that convert potent androgens and estrogens to weak hormones; cytochrome P450 hydroxylating enzymes CYP1A1, CYP1A2, and CYP1B1; and the metabolic enzymes COMT, SULT1A1, and SULT1E1. We observed a significant association of rs11205 in HSD17B4 with TGCT. TGCT risk was increased twofold per copy of the minor A allele at this locus (odds ratios (OR) = 2.273, 95% confidence interval (CI) = 1.737-2.973). Homozygous carriage of the minor A allele was associated with an over fourfold increased risk of TGCT (OR = 4.561, 95% CI = 2.615-7.955) compared with homozygous carriage of the major G allele. The risk was increased both for seminoma (OR = 5.327, 95% CI = 2.857-9.931) and for nonseminoma (OR = 3.222, 95% CI = 1.471-7.059). We found for the first time an association of polymorphisms in HSD17B4 gene with TGCT. Our findings expand the current knowledge on the role of genetic contribution in testicular cancer susceptibility, and support the hypothesis that variations in hormone metabolism genes might change the hormonal environment implicated in testicular carcinogenesis. Endocrine-Related Cancer (2010) 17 17-25