Comprehensive Analysis of Hormone and Genetic Variation in 36 Genes Related to Steroid Hormone Metabolism in Pre- and Postmenopausal Women from the Breast and Prostate Cancer Cohort Consortium (BPC3)
Comprehensive Analysis of Hormone and Genetic Variation in 36 Genes Related to Steroid Hormone Metabolism in Pre- and Postmenopausal Women from the Breast and Prostate Cancer Cohort Consortium (BPC3)
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DOI：
10.1210/jc.2010-0912
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发表时间：
2011-02-01
影响因子：
5.8
通讯作者：
Kaaks, R.
中科院分区：
文献类型：
--
作者：
Beckmann, L.;Husing, A.;Kaaks, R.
背景：性类固醇在乳腺癌的发展中发挥着核心作用。目的：本研究旨在将性类固醇途径中 36 个候选基因的多态性变异与性类固醇激素和性激素结合球蛋白 (SHBG) 的血清浓度联系起来。设计：在欧洲癌症与营养前瞻性调查 (EPIC) 和 护士健康研究 (NHS) 队列；在多种族队列 (MEC) 中重新分析了重要发现。 背景和参与者：我们分析了来自 EPIC 和 NHS 的 3852 名绝经前和绝经后白人女性以及来自 MEC 的 454 名绝经后女性的合并样本的数据。 主要结果指标：结果指标包括性激素结合球蛋白 (SHBG)、睾酮、脱氢表雄酮 (DHEAS)、 雄烯二酮、雌酮 (E1) 和雌二醇 (E2) 以及乳腺癌风险。结果：在绝经前和绝经后女性中，SHBG 与 SHBG 基因水平以及 DHEAS 与 FSHR 和 AKR1C3 基因之间的组合发现具有全球显着关联。在绝经后女性中，血清E1和E2与CYP19和FSHR基因显着相关，E1与ESR1相关。与血清激素水平相关的变异均未显示与乳腺癌风险有任何显着关联。结论：我们证实了 SHBG 与 SHBG 基因以及 E1 和 E2 以及 CYP19 和 ESR1 基因的血清水平之间的关联。在 FSHR 和 DHEAS、E1 和 E2 之间以及 AKR1C3 和 DHEAS 之间观察到新的关联。 （临床内分泌代谢杂志 96：E360-E367，2011）
Context: Sex steroids play a central role in breast cancer development.Objective: This study aimed to relate polymorphic variants in 36 candidate genes in the sex steroid pathway to serum concentrations of sex steroid hormones and SHBG.Design: Data on 700 genetic polymorphisms were combined with existing hormone assays and data on breast cancer incidence, within the European Prospective Investigation into Cancer and Nutrition (EPIC) and the Nurses' Health Study (NHS) cohorts; significant findings were reanalyzed in the Multiethnic Cohort (MEC).Setting and Participants: We analyzed data from a pooled sample of 3852 pre- and postmenopausal Caucasian women from EPIC and NHS and 454 postmenopausal women from MEC.Main Outcome Measures: Outcome measures were SHBG, testosterone, dehydroepiandrosterone (DHEAS), androstenedione, estrone (E1), and estradiol (E2) as well as breast cancer risk.Results: Globally significant associations were found among pre- and postmenopausal women combined between levels of SHBG and the SHBG gene and between DHEAS and the FSHR and AKR1C3 genes. Among postmenopausal women, serum E1 and E2 were significantly associated with the genes CYP19 and FSHR, and E1 was associated with ESR1. None of the variants related to serum hormone levels showed any significant association with breast cancer risk.Conclusions: We confirmed associations between serum levels of SHBG and the SHBG gene and of E1 and E2 and the CYP19 and ESR1 genes. Novel associations were observed between FSHR and DHEAS, E1, and E2 and between AKR1C3 and DHEAS. (J Clin Endocrinol Metab 96: E360-E367, 2011)