CoChat
Sign Up
Cited by 649Selenium in Biological SystemsOrganoselenium and organotellurium chemistryTrace Elements in Health

Selenium for preventing cancer

Open access
Vinceti, Marco, Filippini, Tommaso, Del Giovane, Cinzia, Dennert, Gabriele, Zwahlen, Marcel, Brinkman, Maree, Zeegers, Maurice PA, Horneber, Markus +2 more·2018·Cochrane Database of Systematic Reviews
DOI 10.1002/14651858.cd005195.pub4PMC PMC6491296
Open this paper in CoChat — free accountOpen PDF

Abstract

BACKGROUND: This review is the third update of the Cochrane review "Selenium for preventing cancer". Selenium is a naturally occurring element with both nutritional and toxicological properties. Higher selenium exposure and selenium supplements have been suggested to protect against several types of cancer. OBJECTIVES: To gather and present evidence needed to address two research questions:1. What is the aetiological relationship between selenium exposure and cancer risk in humans?2. Describe the efficacy of selenium supplementation for cancer prevention in humans. SEARCH METHODS: We updated electronic searches of the Cochrane Central Register of Controlled Trials (CENTRAL; 2017, Issue 2), MEDLINE (Ovid, 2013 to January 2017, week 4), and Embase (2013 to 2017, week 6), as well as searches of clinical trial registries. SELECTION CRITERIA: We included randomised controlled trials (RCTs) and longitudinal observational studies that enrolled adult participants. DATA COLLECTION AND ANALYSIS: We performed random-effects (RE) meta-analyses when two or more RCTs were available for a specific outcome. We conducted RE meta-analyses when five or more observational studies were available for a specific outcome. We assessed risk of bias in RCTs and in observational studies using Cochrane's risk assessment tool and the Newcastle-Ottawa Scale, respectively. We considered in the primary analysis data pooled from RCTs with low risk of bias. We assessed the certainty of evidence by using the GRADE approach. MAIN RESULTS: We included 83 studies in this updated review: two additional RCTs (10 in total) and a few additional trial reports for previously included studies. RCTs involved 27,232 participants allocated to either selenium supplements or placebo. For analyses of RCTs with low risk of bias, the summary risk ratio (RR) for any cancer incidence was 1.01 (95% confidence interval (CI) 0.93 to 1.10; 3 studies, 19,475 participants; high-certainty evidence). The RR for estimated cancer mortality was 1.02 (95% CI 0.80 to 1.30; 1 study, 17,444 participants). For the most frequently investigated site-specific cancers, investigators provided little evidence of any effect of selenium supplementation. Two RCTs with 19,009 participants indicated that colorectal cancer was unaffected by selenium administration (RR 0.99, 95% CI 0.69 to 1.43), as were non-melanoma skin cancer (RR 1.16, 95% CI 0.30 to 4.42; 2 studies, 2027 participants), lung cancer (RR 1.16, 95% CI 0.89 to 1.50; 2 studies, 19,009 participants), breast cancer (RR 2.04, 95% CI 0.44 to 9.55; 1 study, 802 participants), bladder cancer (RR 1.07, 95% CI 0.76 to 1.52; 2 studies, 19,009 participants), and prostate cancer (RR 1.01, 95% CI 0.90 to 1.14; 4 studies, 18,942 participants). Certainty of the evidence was high for all of these cancer sites, except for breast cancer, which was of moderate certainty owing to imprecision, and non-melanoma skin cancer, which we judged as moderate certainty owing to high heterogeneity. RCTs with low risk of bias suggested increased melanoma risk.Results for most outcomes were similar when we included all RCTs in the meta-analysis, regardless of risk of bias. Selenium supplementation did not reduce overall cancer incidence (RR 0.99, 95% CI 0.86 to 1.14; 5 studies, 21,860 participants) nor mortality (RR 0.81, 95% CI 0.49 to 1.32; 2 studies, 18,698 participants). Summary RRs for site-specific cancers showed limited changes compared with estimates from high-quality studies alone, except for liver cancer, for which results were reversed.In the largest trial, the Selenium and Vitamin E Cancer Trial, selenium supplementation increased risks of alopecia and dermatitis, and for participants with highest background selenium status, supplementation also increased risk of high-grade prostate cancer. RCTs showed a slightly increased risk of type 2 diabetes associated with supplementation. A hypothesis generated by the Nutritional Prevention of Cancer Trial - that individuals with low blood selenium levels could reduce their risk of cancer (particularly prostate cancer) by increasing selenium intake - has not been confirmed. As RCT participants have been overwhelmingly male (88%), we could not assess the potential influence of sex or gender.We included 15 additional observational cohort studies (70 in total; over 2,360,000 participants). We found that lower cancer incidence (summary odds ratio (OR) 0.72, 95% CI 0.55 to 0.93; 7 studies, 76,239 participants) and lower cancer mortality (OR 0.76, 95% CI 0.59 to 0.97; 7 studies, 183,863 participants) were associated with the highest category of selenium exposure compared with the lowest. Cancer incidence was lower in men (OR 0.72, 95% CI 0.46 to 1.14, 4 studies, 29,365 men) than in women (OR 0.90, 95% CI 0.45 to 1.77, 2 studies, 18,244 women). Data show a decrease in risk of site-specific cancers for stomach, colorectal, lung, breast, bladder, and prostate cancers. However, these studies have major weaknesses d

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1002/14651858.cd005195.pub4

Cites

417 of 417 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 17

  1. Aggett PJ. (2010). Toxicity due to excess and deficiency. J Toxicol Environ Health A: 73(2):175-80.
  2. Derumeaux H, Valeix P, Castetbon K, Bensimon M, Boutron-Ruault MC, Arnaud J, Hercberg S. (2003). Association of selenium with thyroid volume and echostructure in 35-to 60-year-old French adults. Eur J Endocrinol 148(3):309-15.
  3. Douron M. (2010). U-shaped dose-response curves: implications for risk characterization of essential elements and other chemicals. J Toxicol Environ Health A 73(2):181-6.
  4. Ezzedine K, Latreille J, Kesse-Guyot E, Galan P, Hercberg S, Guinot C, Malvy D. (2010). Incidence of skin cancers during 5- year follow-up after stopping antioxidant vitamins and mineral supplementation. Eur J Cancer 46(18):3316-22.
  5. Nogueira CW, Rocha JB. (2011). Toxicology and pharmacology of selenium: emphasis on synthetic organo-selenium compounds. Arch Toxicol 85(11):1313-59.
  6. Renwick AG, Walker R. (2008). Risk assessment of micronutrients.Toxicol Lett 180(2):123-30.
  7. Rothman KJ, Greenland S, Lash TL. (2008). Modern Epidemiology. Philadelphia: Lippincott Williams & Wilkins.
  8. Schrauzer GN, White DA, Schneider CJ. (1977). Cancer mortality correlation studies-IV: associations with dietary intakes and blood levels of certain trace elements, notably Se-antagonists. Bioinorg Chem 7(1):35-56.
  9. Steinbrenner H, Speckmann B, Pinto A, Sies H. (2011). High selenium intake and increased diabetes risk: experimental evidence for interplay between selenium and carbohydrate metabolism. J Clin Biochem Nutr 48(1):40-5.
  10. Vinceti M, Stranges S, Sieri S, Grioni S, Malagoli C, Muti P, Berrino F, Krogh V. (2009b). Association between high selenium intake and subsequent increased risk of type 2 diabetes in an Italian population. ISEE 2009 Conference Abstracts Supplement; Epidemiology: 20: S47.
  11. Contributors Professor Regina Brigelius-Floh, Professor GF Combs Jr, Dr Cindy D Davis, Dr Fiona R Green, Professor John Hesketh, Professor Josef Köhrle, Dr Alan Kristal, Fred Hutchinson, Professor Margaret P Rayman, Professor Lutz Schomburg, Phil Taylor, Piet van den Brandt, Professor David J. Waters, Professor Phil Whanger. Maree Brinkman, Gabriele Dennert and Marco Vinceti on behalf of the review authors. Professor GF Combs Jr, Grand Forks Human Nutrition Research Center, ARS/USDA, USA
  12. MV co-ordinated the current update, commented on the protocol and the review, screened search results, appraised study bias, and updated the draft in collaboration with the other review authors.
  13. TF and CDG extracted data from the added papers, appraised study bias, conducted data analyses, commented on the review, wrote part of the draft, and provided a methodological perspective.
  14. CDG commented on the review, appraised study bias, prepared the 'Summary of findings' (GRADE) table, wrote part of the draft, and provided a methodological perspective.
  15. GD is the primary author of the first version of the review and was involved in all steps of the present update, including commenting on the protocol and the manuscript, extracting data from papers, and providing a methodological perspective.
  16. MZw commented on the protocol and the review and provided a methodological perspective.
  17. MZe commented on the protocol and the review and provided feedback on different portions of these documents.

Cited by

Sorted by citations

Related

Authors
Vinceti, M., Filippini, T., Del Giovane, C., Dennert, G., Zwahlen, M., Brinkman, M., Zeegers, M. P., Horneber, M., D'Amico, R., & Crespi, C. M.
Affiliations
  • Boston University (US)
  • University of Modena and Reggio Emilia (IT)
  • University of Bern; Institute of Primary Health Care (BIHAM); Gesellschaftsstrasse 49 Bern Switzerland 3012
  • Dortmund University of Applied Sciences and Arts (DE)
  • University of Bern (CH)
  • Maastricht University (NL)
  • Maastricht University; Complex Genetics; Maastricht Netherlands
  • Nuremberg Hospital (DE)
  • University of Modena and Reggio Emilia; Cochrane Italy, Department of Diagnostic, Clinical and Public Health Medicine; Via del Pozzo, 71 Modena Italy 41100
  • University of California, Los Angeles (US)
ORCID
Venue
Cochrane Database of Systematic Reviews
Publisher
Wiley
Published
2018-01-29
Volume
2020
Issue
2
Pages
CD005195-CD005195
ISSN
  • 1361-6137 (ISSN-L)
  • 1465-1858
DOI
10.1002/14651858.cd005195.pub4
PMC
PMC6491296
OpenAlex
W3023435860
Cited by
649
References
417
Citations by year
2026: 14 · 2025: 32 · 2024: 50 · 2023: 51 · 2022: 57 · 2021: 71 · 2020: 46 · 2019: 52 · 2018: 49 · 2017: 35 · 2016: 50 · 2015: 31 · 2014: 38 · 2013: 29 · 2012: 29
FWCI
6.99
Type
journal article
Language
en
Open access
Locations
  • Cochrane Database of Systematic Reviews (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • Research Publications (Maastricht University) (publishedVersion, other-oa)
  • BORIS (University Library Bern) (submittedVersion, other-oa)
  • Bern Open Repository and Information System (University of Bern) (submittedVersion, other-oa)
  • eScholarship (California Digital Library) (submittedVersion)
  • IRIS UNIMORE (University of Modena and Reggio Emilia) (submittedVersion, cc-by)
  • Research Publications (Maastricht University) (submittedVersion, other-oa)
Funders
  • Università Degli Studi di Modena e Reggio Emila
  • McMaster University
  • National Institute for Health and Care Research
  • European Commission
  • Deutsche Krebshilfe
  • National Institutes of Health (CA16042)
  • Evidence Synthesis Programme
  • National Cancer Institute (CA-16 042)
  • National Center for Complementary and Alternative Medicine (AT001293)
  • National Center for Complementary and Integrative Health (R24AT001293)
Topics
  • Health Sciences › Nursing › Nutrition and Dietetics › Selenium in Biological Systems
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Toxicology › Organoselenium and organotellurium chemistry
  • Health Sciences › Nursing › Nutrition and Dietetics › Trace Elements in Health
Keywords
selenium supplementation, cancer prevention, selenium exposure, cancer incidence, cancer mortality, colorectal cancer, prostate cancer, breast cancer, lung cancer, selenium toxicity, selenium deficiency
MeSH terms
Female, Humans, Male, Neoplasms, Selenium, Sex Factors, Trace Elements, Odds Ratio, Case-Control Studies, Randomized Controlled Trials as Topic, Observational Studies as Topic

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review