Selenium for preventing cancer

Updated
Authors: 
Vinceti M, Filippini T, Del Giovane C, Dennert G, Zwahlen M, Brinkman M, Zeegers MPA, Horneber M, D'Amico R, Crespi CM

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.

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