Selenium for preventing cancer
Abstract
Background
Selenium is a trace element essential to humans. 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 relationship between selenium exposure and cancer risk in women and men?
2. the efficacy of selenium supplementation for cancer prevention in women and men?
Search methods
We conducted electronic searches in the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library Issue 1, 2011), MEDLINE (via PubMed, 1966 to February 2011), EMBASE (1980 to 2010 week 50), 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.
We also searched the following online clinical trials databases: Clinical Trials of the American Cancer Society, the metaRegister of Controlled Trials (mRCT) and the German Cancer Study Register to February 2011 and conference abstracts to identify unpublished material and searched the database for grey literature SIGLE.
Selection criteria
We included prospective observational studies (cohort studies including sub‐cohort controlled studies and nested case‐control studies) to answer research question (a) and randomised controlled trials (RCTs) to answer research question (b). All adult participants (aged 18 years and over) at risk of malignant neoplastic diseases.
Data collection and analysis
We conducted random effects meta‐analyses of epidemiological data when five or more studies were retrieved for a specific outcome. We made a narrative summary of data from RCTs.
Main results
We included 49 prospective observational studies and six RCTs. In epidemiologic data, we found a reduced cancer incidence (summary odds ratio (OR) 0.69 (95% confidence interval (CI) 0.53 to 0.91) and mortality (OR 0.55, 95% CI 0.36 to 0.83) with higher selenium exposure. Cancer risk was more pronouncedly reduced in men (incidence: OR 0.66, 95% CI 0.42 to 1.05) than in women (incidence: OR 0.90, 95% CI 0.45 to 1.77). These findings have potential limitations due to study design, quality and heterogeneity of the data, which complicated the interpretation of the summary statistics.
The RCTs found no protective efficacy of selenium yeast supplementation against non‐melanoma skin cancer or L‐selenomethionine supplementation against prostate cancer. Study results for the prevention of liver cancer with selenium supplements were inconsistent and studies had an unclear risk of bias. The results of the Nutritional Prevention of Cancer Trial (NPCT) and SELECT raised concerns about possible harmful effects of selenium supplements.
Authors' conclusions
No reliable conclusions can be drawn regarding a causal relationship between low selenium exposure and an increased risk of cancer. Despite evidence for an inverse association between selenium exposure and the risk of some types of cancer, these results should be interpreted with care due to the potential limiting factors of heterogeneity and influences of unknown biases, confounding and effect modification.
The effect of selenium supplementation from RCTs yielded inconsistent results. To date, there is no convincing evidence that selenium supplements can prevent cancer in men, women or children.
PICOs
Plain language summary
Selenium for preventing cancer
Selenium is a trace element that is important for human health, but might also be harmful for humans when the taken in excess.
Fifty‐five studies with more than one million participants were included in this systematic review. Forty‐nine studies observed and analysed whether healthy people with high selenium levels in blood or toenail samples or with a high selenium intake developed cancer more or less often than other people. We found that people with higher selenium levels or intake had a lower frequency of certain cancers (such as bladder or prostate cancer) but no difference for other cancers such as breast cancer. However, it was not possible to determine from these studies that selenium levels or selenium intake were really the reason for the lower risk of cancer in some people. Factors apart from higher selenium levels could also influence the cancer risk: They might have had a healthier nutritional intake or lifestyle, have had a more favourable job or overall living conditions.
Six randomised controlled trials (RCTs) assessed whether the use of selenium supplements might prevent cancer. In general, there are two types of selenium supplements: one type uses the salt of selenium as main ingredient, the other type uses organic selenium. These two types may act differently in the human body when ingested. We assessed the quality of each trial according to four established methodological criteria. The trials with the most reliable results found that organic selenium did not prevent prostate cancer in men and increased the risk of non‐melanoma skin cancer in women and men. Other trials found that participants using selenium salt or organic supplements had a decrease in liver cancer cases. However, due to methodological shortcomings this evidence was less convincing. We advise further investigation of selenium for liver cancer prevention before translating results into public health recommendations. We also recommend that there should be further evaluation of the effects of selenium supplements in populations according to their nutritional status as they may differ between undernourished and adequately nourished groups of people.
To maintain or improve health, access to healthy food and a healthy diet is important. Currently, there is no convincing evidence that individuals, particularly those who are adequately nourished, will benefit from selenium supplementation with regard to their cancer risk.
