Kho Pik Fang, Glubb Dylan M, Thompson Deborah J, Spurdle Amanda B, O'Mara Tracy A
Molecular Cancer Epidemiology Group, Genetics and Computational Biology Department, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.
Department of Public Health and Primary Care, Centre for Cancer Genetic Epidemiology, University of Cambridge, Cambridge, United Kingdom.
Front Oncol. 2019 Mar 27;9:182. doi: 10.3389/fonc.2019.00182. eCollection 2019.
Endometrial cancer is the most commonly diagnosed gynecological cancer in developed countries. Based on evidence from observational studies which suggest selenium inhibits the development of several cancers (including lung and prostate cancer), selenium supplementation has been touted as a potential cancer preventative agent. However, randomized controlled trials have not reported benefit for selenium supplementation in reducing cancer risk. For endometrial cancer, limited observational studies have been conducted assessing whether selenium intake, or blood selenium levels, associated with reduced risk, and no randomized controlled trials have been conducted. We performed a two-sample Mendelian randomization analysis to examine the relationship between selenium levels (using a composite measure of blood and toenail selenium) and endometrial cancer risk, using summary statistics for four genetic variants associated with selenium levels at genome-wide significance levels ( < 5 × 10), from a study of 12,906 endometrial cancer cases and 108,979 controls, all of European ancestry. Inverse variance weighted (IVW) analysis indicated no evidence of a causal role for selenium levels in endometrial cancer development (OR per unit increase in selenium levels Z-score = 0.99, 95% CI = 0.87-1.14). Similar results were observed for sensitivity analyses robust to the presence of unknown pleiotropy (OR per unit increase in selenium levels Z-score = 0.98, 95% CI 0.89-1.08 for weighted median; OR per unit increase in selenium levels Z-score = 0.90, 95% CI = 0.53-1.50 for MR-Egger). In conclusion, these results do not support the use of selenium supplementation to prevent endometrial cancer.
子宫内膜癌是发达国家最常被诊断出的妇科癌症。基于观察性研究的证据表明，硒能抑制多种癌症（包括肺癌和前列腺癌）的发展，补充硒已被吹捧为一种潜在的癌症预防剂。然而，随机对照试验并未报告补充硒在降低癌症风险方面有任何益处。对于子宫内膜癌，评估硒摄入量或血硒水平与降低风险之间关系的观察性研究有限，且尚未进行随机对照试验。我们进行了一项两样本孟德尔随机化分析，以研究硒水平（使用血液和 toenail 硒的综合测量）与子宫内膜癌风险之间的关系，使用了来自一项对 12906 例子宫内膜癌病例和 108979 例对照（均为欧洲血统）的研究中，与全基因组显著水平（<5×10）的硒水平相关的四个基因变异的汇总统计数据。逆方差加权（IVW）分析表明，没有证据表明硒水平在子宫内膜癌发展中起因果作用（硒水平 Z 评分每增加一个单位的 OR = 0.99，95%CI = 0.87 - 1.14）。对于对未知多效性存在具有稳健性的敏感性分析，也观察到了类似结果（加权中位数分析中，硒水平 Z 评分每增加一个单位的 OR = 0.98，95%CI 0.89 - 1.08；MR - Egger 分析中，硒水平 Z 评分每增加一个单位的 OR = 0.90，95%CI = 0.53 - 1.50）。总之，这些结果不支持使用补充硒来预防子宫内膜癌。
