Review question

We reviewed the evidence investigating the relation between selenium intake and cancer prevention. This review updates the most recent Cochrane review on this topic (Vinceti 2014), which was an update of Dennert 2011.

 

Background

Selenium is a naturally occurring element that individuals are exposed to mainly through food consumption, although exposure can also occur through air, drinking water, and dietary supplements. Small amounts of selenium are essential for certain biological functions in humans, but slightly higher amounts can pose a toxicity risk, making selenium an element with a narrow, but as yet not well-defined, safe range of exposure. Selenium occurs in many different chemical forms with different biological activity. From the late 1960s, a few observational studies reported that people with high levels of selenium in their diet or in their body tissues had lower risk of cancer, and some laboratory studies showed that selenium could inhibit the growth of cancer cells. This led to widespread interest in selenium supplements and claims that taking such supplements could prevent cancer. Since that time, many more observational studies have been conducted to compare cancer rates among individuals with high and low selenium exposure. More recently, several randomised controlled trials designed to assess whether selenium supplementation can prevent cancer have been carried out. These trials played a major role in enhancing our understanding of the relation between selenium and cancer risk as a result of their stronger study design as compared with observational studies. The most recent trials in particular have shown high methodological quality and statistical power. Several trials focused on whether selenium could prevent prostate cancer.

Study characteristics

This review includes 10 trials in which adults were randomly assigned to receive selenium supplements or placebo, and 70 observational studies in which adults were followed over time to determine whether their baseline selenium status was associated with their risk of cancer. The evidence is current to January 2017.

Key results

All of the high-quality randomised trials reported no effect of selenium on reducing overall risk of cancer or risk of particular cancers, including the most investigated outcome - prostate cancer. Some trials unexpectedly suggested that selenium may increase risks of high-grade prostate cancer, type 2 diabetes, and dermatological abnormalities. Observational studies have yielded inconsistent evidence of a possible effect of selenium exposure on cancer risk, with no evidence of a dose-response relation. When we pooled results of these studies, overall they suggested an inverse relation between cancer exposure and subsequent incidence of any cancer or some specific cancers, such as colon and prostate cancer. However, observational studies have major weaknesses. The selenium exposure status of participants could have been misclassified owing to limitations of the indicators of selenium exposure used, as well as to uncertainty regarding the particular selenium species contributing to overall exposure. In addition, unmeasured confounding from lifestyle or nutritional factors - a major and well-known source of bias in nutritional epidemiology studies of observational design - could have been present. Therefore, the internal validity of these studies is limited. Currently, the hypothesis that increasing selenium intake may reduce cancer risk is not supported by epidemiological evidence. Additional research is needed to assess whether selenium may affect the risk of cancer in individuals with specific genetic backgrounds or nutritional status, and to determine how the various chemical forms of selenium compounds may have different effects on cancer risk.

Authors' conclusions: 

Well-designed and well-conducted RCTs have shown no beneficial effect of selenium supplements in reducing cancer risk (high certainty of evidence). Some RCTs have raised concerns by reporting a higher incidence of high-grade prostate cancer and type 2 diabetes in participants with selenium supplementation. No clear evidence of an influence of baseline participant selenium status on outcomes has emerged in these studies. Observational longitudinal studies have shown an inverse association between selenium exposure and risk of some cancer types, but null and direct relations have also been reported, and no systematic pattern suggesting dose-response relations has emerged. These studies suffer from limitations inherent to the observational design, including exposure misclassification and unmeasured confounding. Overall, there is no evidence to suggest that increasing selenium intake through diet or supplementation prevents cancer in humans. However, more research is needed to assess whether selenium may modify the risk of cancer in individuals with a specific genetic background or nutritional status, and to investigate possible differential effects of various forms of selenium.