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Review
. 2014 Mar 30;2014(3):CD005195.
doi: 10.1002/14651858.CD005195.pub3.

Selenium for Preventing Cancer

Affiliations
Free PMC article
Review

Selenium for Preventing Cancer

Marco Vinceti et al. Cochrane Database Syst Rev. .
Free PMC article

Update in

  • Selenium for preventing cancer.
    Vinceti M, Filippini T, Del Giovane C, Dennert G, Zwahlen M, Brinkman M, Zeegers MP, Horneber M, D'Amico R, Crespi CM. Vinceti M, et al. Cochrane Database Syst Rev. 2018 Jan 29;1(1):CD005195. doi: 10.1002/14651858.CD005195.pub4. Cochrane Database Syst Rev. 2018. PMID: 29376219 Free PMC article. Review.

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? and2. the efficacy of selenium supplementation for cancer prevention in humans?

Search methods: 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.

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.

Conflict of interest statement

MV: None known.

GD: None known.

CMC: None known.

MZw: None known.

MB: None known.

MZe: Maurice Zeegers is the first investigator of one included observational study and one ongoing randomised controlled trial. He is second author of another included observational study.

MH: None known.

RDA: None known.

CDG: None known.

Figures

Figure 1
Figure 1
Flow chart.
Figure 2
Figure 2
Newcastle‐Ottawa Scale: number of studies by number of "stars" assigned in the case‐control portion of studies.
Figure 3
Figure 3
Newcastle‐Ottawa Scale: number of studies by number of "stars" assigned in the cohort portion of studies.
Figure 4
Figure 4
Funnel plot of comparison: 1 Highest versus lowest selenium exposure, outcome: 1.17 Total cancer incidence and mortality.
Figure 5
Figure 5
Funnel plot of comparison: 1 Highest versus lowest selenium exposure, outcome: 1.7 Prostate cancer risk.
Analysis 1.1
Analysis 1.1
Comparison 1 Observational studies: highest versus lowest selenium exposure, Outcome 1 Total cancer incidence and mortality.
Analysis 1.2
Analysis 1.2
Comparison 1 Observational studies: highest versus lowest selenium exposure, Outcome 2 Total cancer incidence and mortality (men).
Analysis 1.3
Analysis 1.3
Comparison 1 Observational studies: highest versus lowest selenium exposure, Outcome 3 Total cancer incidence and mortality (women).
Analysis 1.4
Analysis 1.4
Comparison 1 Observational studies: highest versus lowest selenium exposure, Outcome 4 Total cancer incidence and mortality (ascending order of selenium levels).
Analysis 1.5
Analysis 1.5
Comparison 1 Observational studies: highest versus lowest selenium exposure, Outcome 5 Breast cancer risk (women).
Analysis 1.6
Analysis 1.6
Comparison 1 Observational studies: highest versus lowest selenium exposure, Outcome 6 Bladder cancer risk.
Analysis 1.7
Analysis 1.7
Comparison 1 Observational studies: highest versus lowest selenium exposure, Outcome 7 Lung cancer risk (gender‐aggregated data).
Analysis 1.8
Analysis 1.8
Comparison 1 Observational studies: highest versus lowest selenium exposure, Outcome 8 Lung cancer risk (gender‐disaggregated data).
Analysis 1.9
Analysis 1.9
Comparison 1 Observational studies: highest versus lowest selenium exposure, Outcome 9 Lung cancer risk.
Analysis 1.10
Analysis 1.10
Comparison 1 Observational studies: highest versus lowest selenium exposure, Outcome 10 Lung cancer risk (ascending order of selenium levels).
Analysis 1.11
Analysis 1.11
Comparison 1 Observational studies: highest versus lowest selenium exposure, Outcome 11 Prostate cancer risk.
Analysis 1.12
Analysis 1.12
Comparison 1 Observational studies: highest versus lowest selenium exposure, Outcome 12 Prostate cancer risk (by selenium measurement).
Analysis 1.13
Analysis 1.13
Comparison 1 Observational studies: highest versus lowest selenium exposure, Outcome 13 Prostate cancer risk (by exposure assessment).
Analysis 1.14
Analysis 1.14
Comparison 1 Observational studies: highest versus lowest selenium exposure, Outcome 14 Prostate cancer risk (by continent).
Analysis 1.15
Analysis 1.15
Comparison 1 Observational studies: highest versus lowest selenium exposure, Outcome 15 Prostate cancer risk (by country).
Analysis 1.16
Analysis 1.16
Comparison 1 Observational studies: highest versus lowest selenium exposure, Outcome 16 Prostate cancer risk (ascending order of selenium levels).
Analysis 1.17
Analysis 1.17
Comparison 1 Observational studies: highest versus lowest selenium exposure, Outcome 17 Stomach cancer risk.
Analysis 1.18
Analysis 1.18
Comparison 1 Observational studies: highest versus lowest selenium exposure, Outcome 18 Stomach cancer risk (by gender).
Analysis 1.19
Analysis 1.19
Comparison 1 Observational studies: highest versus lowest selenium exposure, Outcome 19 Colorectal cancer risk.
Analysis 1.20
Analysis 1.20
Comparison 1 Observational studies: highest versus lowest selenium exposure, Outcome 20 Colorectal cancer risk (by gender).
Analysis 2.1
Analysis 2.1
Comparison 2 Randomised controlled trials: highest versus lowest selenium exposure, Outcome 1 Any cancer risk.
Analysis 2.2
Analysis 2.2
Comparison 2 Randomised controlled trials: highest versus lowest selenium exposure, Outcome 2 Cancer mortality.
Analysis 2.3
Analysis 2.3
Comparison 2 Randomised controlled trials: highest versus lowest selenium exposure, Outcome 3 Liver cancer risk.
Analysis 2.4
Analysis 2.4
Comparison 2 Randomised controlled trials: highest versus lowest selenium exposure, Outcome 4 Non‐melanoma skin cancer risk.
Analysis 2.5
Analysis 2.5
Comparison 2 Randomised controlled trials: highest versus lowest selenium exposure, Outcome 5 Prostate cancer risk.
Analysis 2.6
Analysis 2.6
Comparison 2 Randomised controlled trials: highest versus lowest selenium exposure, Outcome 6 Prostate cancer risk for studies with low RoB.
Analysis 2.7
Analysis 2.7
Comparison 2 Randomised controlled trials: highest versus lowest selenium exposure, Outcome 7 Lung cancer risk.
Analysis 2.8
Analysis 2.8
Comparison 2 Randomised controlled trials: highest versus lowest selenium exposure, Outcome 8 Bladder cancer risk.
Analysis 2.9
Analysis 2.9
Comparison 2 Randomised controlled trials: highest versus lowest selenium exposure, Outcome 9 Colorectal cancer risk.

Update of

  • Selenium for preventing cancer.
    Dennert G, Zwahlen M, Brinkman M, Vinceti M, Zeegers MP, Horneber M. Dennert G, et al. Cochrane Database Syst Rev. 2011 May 11;(5):CD005195. doi: 10.1002/14651858.CD005195.pub2. Cochrane Database Syst Rev. 2011. PMID: 21563143 Free PMC article. Updated. Review.

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