Selenoprotein Gene Variants, Toenail Selenium Levels, and Risk for Advanced Prostate Cancer
Selenoprotein Gene Variants, Toenail Selenium Levels, and Risk for Advanced Prostate Cancer
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DOI：
10.1093/jnci/dju003
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发表时间：
2014-03-01
影响因子：
10.3
通讯作者：
Verhage, Bas A. J.
中科院分区：
文献类型：
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作者：
Geybels, Milan S.;van den Brandt, Piet A.;Verhage, Bas A. J.
较低的硒水平与前列腺癌（PCa）风险增加有关，而硒蛋白基因硒蛋白P（SEPP 1）和谷胱甘肽过氧化物酶1（GPX 1）的遗传变异被认为改变了这种关系。我们调查了在荷兰前瞻性队列研究中趾甲硒水平与晚期前列腺癌风险之间的关联是否被SEPP 1和GPX 1的常见遗传变异所改变。剪下的趾甲被用来测定硒水平和分离DNA用于基因分型。该病例队列研究包括817例晚期PCa病例受试者和1048名亚队列成员，采用考克斯回归模型进行分析。所有统计检验均为双侧检验。三种遗传变异与晚期（III/IV或IV期）PCa风险相关：SEPP 1 rs7579（风险较低; P趋势= .01），GPX 1 rs 17650792（风险较高; P趋势= .03）和GPX 1 rs 1800668（风险较低; P趋势= .005）。趾甲硒水平与晚期前列腺癌风险呈负相关，独立于SEPP 1和GPX 1的常见遗传变异。
Lower selenium levels have been associated with increased risk of prostate cancer (PCa), and genetic variation in the selenoprotein genes selenoprotein P (SEPP1) and glutathione peroxidase 1 (GPX1) is thought to modify this relationship. We investigated whether the association between toenail selenium levels and advanced PCa risk in the prospective Netherlands Cohort Study is modified by common genetic variation in SEPP1 and GPX1. Toenail clippings were used to determine selenium levels and to isolate DNA for genotyping. This case-cohort study, which included 817 case subjects with advanced PCa and 1048 subcohort members, was analyzed with Cox regression models. All statistical tests were two-sided. Three genetic variants were associated with advanced (stage III/IV or IV) PCa risk: SEPP1 rs7579 (lower risk; P-trend = .01), GPX1 rs17650792 (higher risk; P-trend = .03), and GPX1 rs1800668 (lower risk; P-trend = .005). Toenail selenium levels were inversely associated with advanced PCa risk, independently of common genetic variation in SEPP1 and GPX1.