Circulating Selenium and Prostate Cancer Risk: A Mendelian Randomization Analysis.
Circulating Selenium and Prostate Cancer Risk: A Mendelian Randomization Analysis.
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DOI：
10.1093/jnci/djy081
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发表时间：
2018-09-01
期刊：
影响因子：
--
通讯作者：
Martin RM
中科院分区：
文献类型：
--
作者：
Yarmolinsky J;Bonilla C;Haycock PC;Langdon RJQ;Lotta LA;Langenberg C;Relton CL;Lewis SJ;Evans DM;PRACTICAL Consortium;Davey Smith G;Martin RM
在硒和维生素E癌症预防试验（SELECT）中，补充硒（导致循环硒中位数增加114 μg/L）并没有降低前列腺癌的总体风险，但增加了高级别前列腺癌和2型糖尿病的风险。孟德尔随机化分析使用遗传变异来代替可改变的危险因素，可以在观察性研究中加强因果推理。我们构建了一个遗传工具，包含11个单核苷酸多态性，在全基因组关联研究中与循环硒密切相关（P < 5 × 10-8）。在一项对PRACTICAL协会72 729名男性（44 825名病例组，27 904名对照组）的孟德尔随机分析中，114 μg/L的遗传性循环硒升高与前列腺癌无关（优势比[OR] = 1.01, 95%可信区间[CI] = 0.89 ~ 1.13）。与SELECT研究结果一致，硒与晚期（包括高级别）前列腺癌（OR = 1.21, 95% CI = 0.98 - 1.49）和2型糖尿病（OR = 1.18, 95% CI = 0.97 - 1.43）和2型糖尿病（OR = 1.18, 95% CI = 0.97 - 1.43）弱相关，该研究纳入了49 266例受试者和249 906例对照受试者)。我们的孟德尔随机分析不支持补充硒在前列腺癌预防中的作用，并表明补充硒可能对晚期前列腺癌和2型糖尿病的风险有不利影响。
In the Selenium and Vitamin E Cancer Prevention Trial (SELECT), selenium supplementation (causing a median 114 μg/L increase in circulating selenium) did not lower overall prostate cancer risk, but increased risk of high-grade prostate cancer and type 2 diabetes. Mendelian randomization analysis uses genetic variants to proxy modifiable risk factors and can strengthen causal inference in observational studies. We constructed a genetic instrument comprising 11 single nucleotide polymorphisms robustly (P < 5 × 10-8) associated with circulating selenium in genome-wide association studies. In a Mendelian randomization analysis of 72 729 men in the PRACTICAL Consortium (44 825 case subjects, 27 904 control subjects), 114 μg/L higher genetically elevated circulating selenium was not associated with prostate cancer (odds ratio [OR] = 1.01, 95% confidence interval [CI] = 0.89 to 1.13). In concordance with findings from SELECT, selenium was weakly associated with advanced (including high-grade) prostate cancer (OR = 1.21, 95% CI = 0.98 to 1.49) and type 2 diabetes (OR = 1.18, 95% CI = 0.97 to 1.43; in a type 2 diabetes genome-wide association study meta-analysis with up to 49 266 case subjects and 249 906 control subjects). Our Mendelian randomization analyses do not support a role for selenium supplementation in prostate cancer prevention and suggest that supplementation could have adverse effects on risks of advanced prostate cancer and type 2 diabetes.
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