Effect modification of endocrine disruptors and testicular germ cell tumour risk by hormone-metabolizing genes.
Effect modification of endocrine disruptors and testicular germ cell tumour risk by hormone-metabolizing genes.
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DOI：
10.1111/j.1365-2605.2009.00975.x
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发表时间：
2010-08-01
影响因子：
--
通讯作者：
McGlynn KA
中科院分区：
文献类型：
--
作者：
Chia VM;Li Y;Quraishi SM;Graubard BI;Figueroa JD;Weber JP;Chanock SJ;Rubertone MV;Erickson RL;McGlynn KA
据推测，睾丸生殖细胞肿瘤（TGCT）患病率的增加可能归因于内分泌干扰化学物质，例如持久性有机污染物（POP）；这些可能受到激素代谢酶的调节。利用参加美国军人睾丸肿瘤环境和内分泌决定因素研究的 568 例病例和 698 名对照者的数据，我们检查了 TGCT 与 POP 之间的关联，包括对，对'-DDE、氯丹相关化合物和多氯联苯 (PCB)，并通过 5 个激素代谢基因的多态性进行修饰 （CYP17A1、CYP1A1、HSD17B1、HSD17B4 和 AR）。使用逻辑回归模型估计优势比 (OR) 和 95% 置信区间 (CI)，该模型按基因型对 POP 暴露与 TGCT 风险之间的关联进行分层。 CYP1A1 的两个多态性（rs1456432 和 rs7495708）改变了反式九氯丹和总氯丹与 TGCT 风险之间的关联。在具有 rs1456432 次要等位基因的男性中，与具有最低四分位数的人相比，具有最高四分位数的人患 TGCT 的风险更高（OR=1.90，95% CI，1.01–3.56）；具有纯合主要等位基因基因型的男性没有增加风险（p-相互作用=0.024）。 rs7495708 也出现了类似的结果。 HSD17B4 rs384346 改变了 TGCT 风险与 PCB-118 和 PCB-138 浓度之间的关联：与最低四分位数的男性相比，具有最高四分位数的男性 TGCT 风险降低 45-55%，仅存在于具有主要纯合等位基因基因型的男性中（p 相互作用 <0.04）。因此，有人建议某些 CYP1A1 和 HSD17B4 多态性可能会改变 POP 与 TGCT 风险之间的关联。然而，由于错误发现率值 >0.2，因此在解释本研究结果时应谨慎行事。
It has been hypothesized that the increased prevalence of testicular germ cell tumors (TGCT) may be attributable to endocrine disrupting chemicals, such as persistent organic pollutants (POPs); these may be modulated by hormone-metabolizing enzymes. Using data from 568 cases and 698 controls enrolled in the U.S. Servicemen’s Testicular Tumor Environmental and Endocrine Determinants Study, we examined associations between TGCT and POPs, including p,p′-DDE, chlordane-related compounds, and polychlorinated biphenyls (PCBs), modified by polymorphisms in 5 hormone-metabolizing genes (CYP17A1, CYP1A1, HSD17B1, HSD17B4, and AR). Odds ratios (OR) and 95% confidence intervals (CI) were estimated using logistic regression models that stratified associations of POP exposure and TGCT risk by genotype. Two polymorphisms in CYP1A1, rs1456432 and rs7495708, modified the association between trans-nonachlor and total chlordanes and TGCT risk. Among men with a minor allele for rs1456432, those with the highest quartiles had an increased risk of TGCT (OR=1.90, 95% CI, 1.01–3.56) compare to those with the lowest; there were no increased risk among men with the homozygous major allele genotype (p-interaction=0.024). Similar results were seen for rs7495708. HSD17B4 rs384346 modified the associations between TGCT risk and PCB-118 and PCB-138 concentrations: the 45–55% reductions in TGCT risk for men with the highest quartiles compared to the lowest quartiles were only present in those who had a major homozygous allele genotype (p-interactions<0.04). Thus, there are suggestions that certain CYP1A1 and HSD17B4 polymorphisms may modify the associations between POPs and TGCT risk. With false discovery rate values >0.2, however, caution is advisable when interpreting the findings of this study.
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影响因子：
4
作者：
PHILLIPS, DL;PIRKLE, JL;NEEDHAM, LL
通讯作者：
NEEDHAM, LL
影响因子：
3.2
作者：
Li, Lih-Ann
通讯作者：
Li, Lih-Ann
影响因子：
--
作者：
Skakkebæk, NE
通讯作者：
Skakkebæk, NE
影响因子：
5
作者：
Zhang, YW;Wise, JP;Zheng, TZ
通讯作者：
Zheng, TZ
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y