Selenium for preventing cancer

Review question

We reviewed the evidence suggesting that selenium can help to prevent cancer. This review updates the first Cochrane review on this topic (Dennert 2011).

Background

Selenium is a naturally occurring element found in crops, animal products and water. Small amounts of selenium are needed for proper human nutrition. Starting in the 1960s, numerous studies reported that people with high levels of selenium in their diet or in their body tissues had lower rates of cancer. Some laboratory studies also suggested that selenium could inhibit the growth of cancer cells. This led to widespread interest and claims that taking selenium supplements could prevent cancer. Over the next decades, many more studies were conducted to compare cancer rates among individuals with high and low selenium levels, and several trials were conducted in which individuals were randomly assigned to receive selenium supplements or placebo and then were followed so their cancer rates could be determined. Particular interest focused on whether selenium could prevent prostate, skin or other specific types of cancer.

Study characteristics

This review includes 55 studies in which adults observed to have high or low selenium levels were followed over time to determine whether they developed cancer, along with eight trials in which adults were randomly assigned to receive selenium supplements or placebo. The evidence is current to February 2013.

Key results

We found limited evidence suggesting that individuals observed to have higher selenium levels have a lower incidence of cancer. However, it is not possible to conclude from these studies that selenium was the reason for the lower cancer risk, because a high selenium level might be associated with other factors that reduce cancer risk, such as a healthier diet or lifestyle. Also, selenium comes in many different chemical forms that have different biological activity, and these studies did not identify which chemical forms were being measured. Selenium levels in body tissues in which people might develop cancer (e.g. the prostate) also were not examined.

The randomised controlled trials that assessed whether taking selenium supplements might prevent cancer differed considerably in methodological quality and are not equally reliable. Several studies reported that individuals receiving selenium supplements decreased their liver cancer risk, but these studies reported insufficient details about their randomisation process and participant follow-up to be convincing. Recent trials that were judged to be well conducted and reliable have found no effects of selenium on reducing the overall risk of cancer or on reducing the risk of particular cancers, including prostate cancer. In contrast, some trials suggest that selenium may increase the risk of non-melanoma skin cancer, as well as of type 2 diabetes, raising concern about the safety of selenium supplements.

Overall, no convincing evidence suggests that selenium supplements can prevent cancer. However, for a full understanding of the role of this metalloid in cancer development, more research is needed on how selenium may act differently in individuals with different genetic backgrounds or nutritional status, and on the different biological activities of the various selenium compounds, which are still largely unknown.

Authors' conclusions: 

Although an inverse association between selenium exposure and the risk of some types of cancer was found in some observational studies, this cannot be taken as evidence of a causal relation, and these results should be interpreted with caution. These studies have many limitations, including issues with assessment of exposure to selenium and to its various chemical forms, heterogeneity, confounding and other biases. Conflicting results including inverse, null and direct associations have been reported for some cancer types.

RCTs assessing the effects of selenium supplementation on cancer risk have yielded inconsistent results, although the most recent studies, characterised by a low risk of bias, found no beneficial effect on cancer risk, more specifically on risk of prostate cancer, as well as little evidence of any influence of baseline selenium status. Rather, some trials suggest harmful effects of selenium exposure. To date, no convincing evidence suggests that selenium supplements can prevent cancer in humans.

Read the full abstract...
Background: 

This review is an update of the first Cochrane publication on selenium for preventing cancer (Dennert 2011).

Selenium is a metalloid with both nutritional and toxicological properties. Higher selenium exposure and selenium supplements have been suggested to protect against several types of cancers.

Objectives: 

Two research questions were addressed in this review: What is the evidence for:

1. an aetiological relation between selenium exposure and cancer risk in humans? and
2. the efficacy of selenium supplementation for cancer prevention in humans?

Search strategy: 

We conducted electronic searches of the Cochrane Central Register of Controlled Trials (CENTRAL, 2013, Issue 1), MEDLINE (Ovid, 1966 to February 2013 week 1), EMBASE (1980 to 2013 week 6), CancerLit (February 2004) and CCMed (February 2011). As MEDLINE now includes the journals indexed in CancerLit, no further searches were conducted in this database after 2004.

Selection criteria: 

We included prospective observational studies (cohort studies including sub-cohort controlled studies and nested case-control studies) and randomised controlled trials (RCTs) with healthy adult participants (18 years of age and older).

Data collection and analysis: 

For observational studies, we conducted random effects meta-analyses when five or more studies were retrieved for a specific outcome. For RCTs, we performed random effects meta-analyses when two or more studies were available. The risk of bias in observational studies was assessed using forms adapted from the Newcastle-Ottawa Quality Assessment Scale for cohort and case-control studies; the criteria specified in the Cochrane Handbook for Systematic Reviews of Interventions were used to evaluate the risk of bias in RCTs.

Main results: 

We included 55 prospective observational studies (including more than 1,100,000 participants) and eight RCTs (with a total of 44,743 participants). For the observational studies, we found lower cancer incidence (summary odds ratio (OR) 0.69, 95% confidence interval (CI) 0.53 to 0.91, N = 8) and cancer mortality (OR 0.60, 95% CI 0.39 to 0.93, N = 6) associated with higher selenium exposure. Gender-specific subgroup analysis provided no clear evidence of different effects in men and women (P value 0.47), although cancer incidence was lower in men (OR 0.66, 95% CI 0.42 to 1.05, N = 6) than in women (OR 0.90, 95% CI 0.45 to 1.77, N = 2). The most pronounced decreases in risk of site-specific cancers were seen for stomach, bladder and prostate cancers. However, these findings have limitations due to study design, quality and heterogeneity that complicate interpretation of the summary statistics. Some studies suggested that genetic factors may modify the relation between selenium and cancer risk—a hypothesis that deserves further investigation.

In RCTs, we found no clear evidence that selenium supplementation reduced the risk of any cancer (risk ratio (RR) 0.90, 95% CI 0.70 to 1.17, two studies, N = 4765) or cancer-related mortality (RR 0.81, 95% CI 0.49 to 1.32, two studies, N = 18,698), and this finding was confirmed when the analysis was restricted to studies with low risk of bias. The effect on prostate cancer was imprecise (RR 0.90, 95% CI 0.71 to 1.14, four studies, N = 19,110), and when the analysis was limited to trials with low risk of bias, the interventions showed no effect (RR 1.02, 95% CI 0.90 to 1.14, three studies, N = 18,183). The risk of non-melanoma skin cancer was increased (RR 1.44, 95% CI 0.95 to 1.17, three studies, N = 1900). Results of two trials—the Nutritional Prevention of Cancer Trial (NPCT) and the Selenium and Vitamin E Cancer Trial (SELECT)—also raised concerns about possible increased risk of type 2 diabetes, alopecia and dermatitis due to selenium supplements. An early hypothesis generated by NPCT that individuals with the lowest blood selenium levels at baseline could reduce their risk of cancer, particularly of prostate cancer, by increasing selenium intake has not been confirmed by subsequent trials. As the RCT participants were overwhelmingly male (94%), gender differences could not be systematically assessed.

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