Selenium status is associated with colorectal cancer risk in the European prospective investigation of cancer and nutrition cohort

Abstract

Suboptimal intakes of the micronutrient selenium (Se) are found in many parts of Europe. Low Se status may contribute to colorectal cancer (CRC) development. We assessed Se status by measuring serum levels of Se and Selenoprotein P (SePP) and examined the association with CRC risk in a nested case–control design (966 CRC cases; 966 matched controls) within the European Prospective Investigation into Cancer and Nutrition. Se was measured by total reflection X‐ray fluorescence and SePP by immunoluminometric sandwich assay. Multivariable incidence rate ratios (IRRs) and 95% confidence intervals (CIs) were calculated using conditional logistic regression. Respective mean Se and SePP levels were 84.0 μg/L and 4.3 mg/L in cases and 85.6 μg/L and 4.4 mg/L in controls. Higher Se concentrations were associated with a non‐significant lower CRC risk (IRR = 0.92, 95% CI: 0.82–1.03 per 25 μg/L increase). However, sub‐group analyses by sex showed a statistically significant association for women (ptrend = 0.032; per 25 μg/L Se increase, IRR = 0.83, 95% CI: 0.70–0.97) but not for men. Higher SePP concentrations were inversely associated with CRC risk (ptrend = 0.009; per 0.806 mg/L increase, IRR = 0.89, 95% CI: 0.82–0.98) with the association more apparent in women (ptrend = 0.004; IRR = 0.82, 95% CI: 0.72–0.94 per 0.806 mg/L increase) than men (ptrend = 0.485; IRR = 0.98, 95% CI: 0.86–1.12 per 0.806 mg/L increase). The findings indicate that Se status is suboptimal in many Europeans and suggest an inverse association between CRC risk and higher serum Se status, which is more evident in women.

Gamma radiation at a human relevant low dose rate is genotoxic in mice

“…We have recently shown that the levels of DNA lesions in lung and testis of Se depleted mice were also elevated17. Furthermore, low Se blood levels have been associated with increased risk of cancers such as prostate cancer36, lung cancer37 and colorectal cancer38.…”

Modeling and gene knockdown to assess the contribution of nonsense-mediated decay, premature termination, and selenocysteine insertion to the selenoprotein hierarchy

“…A colon adenocarcinoma cell line (Caco-2) was chosen as the experimental model system since these cells have previously been found to exhibit appropriate hierarchical regulation (Pagmantidis et al 2005) and dietary Se levels have been implicated in colorectal cancer risk (Hughes et al 2015). Expression of selenoprotein mRNAs in Caco-2 cells grown under different Se conditions (from Se deficiency to Se repletion) was determined experimentally and used to build mathematical models of selenoprotein translation that incorporated the different processes likely to be involved in determining the selenoprotein mRNA hierarchy.…”

Epigenetic effects of selenium and their implications for health

“…36 VHL is frequently downregulated and mutated in renal cell carcinomas and also found to be deregulated during colorectal carcinogenesis, 37 wherein Se has been attributed protective functions based on epidemiological and animal studies. 18,38 A study with humans assessed the methylation status of colorectal cancer-related genes in healthy rectal mucosa specimens (84 males, 101 females) in relation to Se status. 39 An association was found for WIF1 (wnt inhibitory factor 1) methylation and plasma Se concentration.…”

“…The EPIC (European prospective investigation of cancer and nutrition cohort) study revealed an inverse association of Se status and colorectal cancer risk with the association being stronger in women than men. 38 Gender-specific effects of Se are also apparent from different responses of selenoprotein expression levels and biomarkers of Se status to Se supplementation in men and women (summarized in 38 ); the study by Tapp et al suggests that this gender-specificity of Se-effects extends to epigenetic marks of cancer-related genes, but the relevance of these findings for disease etiology warrants further investigations. A recent study identified the inflammatory-related genes TLR2 (toll-like receptor 2) and ICAM1 (intercellular adhesion molecule 1) as novel targets of Se-dependent epigenetic regulation and proposed a mechanism whereby Se changes the expression of GADD45 (growth arrest and DNAdamage-inducible, a) and DNMT1, leading to epigenetic silencing of TLR2 and ICAM1, and links it to a well-known condition that arises from prolonged periods of severely deficient Se intake: Keshan disease (K D ).…”