Abstract
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 (P < 5 × 10−8), 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.
Highlights
Endometrial cancer is the most commonly diagnosed cancer of the female reproductive system in developed countries [1]
Mendelian randomization analysis did not support an association between selenium levels and endometrial cancer risk using the inverse variance weighted (IVW) method (OR per unit increase in selenium levels Z-score = 0.99, 95% CI = 0.87–1.14, P = 0.93)
Association estimates from sensitivity analyses (MR-Egger regression and weighted median analysis) were consistent with that reported by IVW analysis (OR per unit increase in selenium levels Z-score = 0.90, 95% CI = 0.53– 1.50, P = 0.72 for MR-Egger; OR per unit increase in selenium levels Z-score = 0.98, 95% CI = 0.89–1.08, P = 0.70 for weighted median)
Summary
Endometrial cancer is the most commonly diagnosed cancer of the female reproductive system in developed countries [1]. Selenium has received considerable attention as a possible cancer preventive agent [reviewed in [4]]. While randomized controlled trials have shown no benefit for selenium supplementation in reducing cancer risk over a period of up to 8 years [5], some observational longitudinal studies assessing. Selenium Levels and Endometrial Cancer Risk selenium intake or selenium levels, over a period up to 25 years, have shown an inverse association between selenium and cancer risk [reviewed in [4]]. A recent meta-analysis examining the association between selenium intake (dietary and supplemental) and overall cancer risk, has suggested that there was a reduction in cancer incidence among people consuming more than the recommended daily allowance of selenium (55 μg/day; RR = 0.96, 95% CI = 0.92– 0.99) [6]
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