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Meta-Analysis
. 2018 Jan 29;1(1):CD005195.
doi: 10.1002/14651858.CD005195.pub4.

Selenium for preventing cancer

Marco Vinceti  1 , Tommaso Filippini, Cinzia Del Giovane, Gabriele Dennert, Marcel Zwahlen, Maree Brinkman, Maurice Pa Zeegers, Markus Horneber, Roberto D'Amico, Catherine M Crespi
Affiliations
Meta-Analysis

Selenium for preventing cancer

Marco Vinceti et al. Cochrane Database Syst Rev. .

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 due to study design, exposure misclassification, and potential unmeasured confounding due to lifestyle or nutritional factors covarying with selenium exposure beyond those taken into account in multi-variable analyses. In addition, no evidence of a dose-response relation between selenium status and cancer risk emerged. Certainty of evidence was very low for each outcome. Some studies suggested that genetic factors might modify the relation between selenium and cancer risk - an issue that merits further investigation.

Authors' conclusions: Well-designed and well-conducted RCTs have shown no beneficial effect of selenium supplements in reducing cancer risk (high certainty of evidence). Some RCTs have raised concerns by reporting a higher incidence of high-grade prostate cancer and type 2 diabetes in participants with selenium supplementation. No clear evidence of an influence of baseline participant selenium status on outcomes has emerged in these studies.Observational longitudinal studies have shown an inverse association between selenium exposure and risk of some cancer types, but null and direct relations have also been reported, and no systematic pattern suggesting dose-response relations has emerged. These studies suffer from limitations inherent to the observational design, including exposure misclassification and unmeasured confounding.Overall, there is no evidence to suggest that increasing selenium intake through diet or supplementation prevents cancer in humans. However, more research is needed to assess whether selenium may modify the risk of cancer in individuals with a specific genetic background or nutritional status, and to investigate possible differential effects of various forms of selenium.

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Conflict of interest statement

  1. MV: none known.

  2. TF: none known.

  3. CDG: none known.

  4. GD: none known.

  5. MZw: none known.

  6. MB: none known.

  7. MZe: Maurice Zeegers is the first investigator and the coauthor of included observational and experimental studies.

  8. MH: none known.

  9. RDA: none known.

  10. CMC: none known.

Figures

1
1
Flow chart.
2
2
Review authors’ judgements about each risk of bias item presented as percentages across all included RCTs and summary of review authors’ judgements about each risk of bias item for the included RCTs.
3
3
Funnel plot of comparison: 1 Highest versus lowest selenium exposure, outcome: 2.1 Total cancer incidence and mortality.
4
4
Funnel plot of comparison: 1 Observational studies: highest versus lowest selenium exposure, outcome: 2.8 Colorectal cancer risk.
5
5
Funnel plot of comparison: 1 Observational studies: highest versus lowest selenium exposure, outcome: 2.12 Lung cancer risk incidence and mortality
6
6
Funnel plot of comparison: 1 Highest versus lowest selenium exposure, outcome: 2.19 Prostate cancer risk.
7
7
Baseline circulating selenium levels in the NPC trial (Duffield‐Lillico 2003b in: NPCT 2002), the NBT (Algotar 2013), SWOG trial (as plasma selenium) (Marshall 2011), and SELECT (as serum selenium) (Lippman 2009, in: SELECT 2009). When median and interquartile values were reported, we estimated mean and standard deviation according to Cochrane guidelines provided in Higgins 2011a.
1.1
1.1. Analysis
Comparison 1 Randomised controlled trials: highest versus lowest selenium exposure, Outcome 1 Any cancer risk.
1.2
1.2. Analysis
Comparison 1 Randomised controlled trials: highest versus lowest selenium exposure, Outcome 2 Cancer mortality.
1.3
1.3. Analysis
Comparison 1 Randomised controlled trials: highest versus lowest selenium exposure, Outcome 3 Head and neck cancer risk.
1.4
1.4. Analysis
Comparison 1 Randomised controlled trials: highest versus lowest selenium exposure, Outcome 4 Oesophageal cancer risk.
1.5
1.5. Analysis
Comparison 1 Randomised controlled trials: highest versus lowest selenium exposure, Outcome 5 Colorectal cancer risk.
1.6
1.6. Analysis
Comparison 1 Randomised controlled trials: highest versus lowest selenium exposure, Outcome 6 Liver cancer risk.
1.7
1.7. Analysis
Comparison 1 Randomised controlled trials: highest versus lowest selenium exposure, Outcome 7 Melanoma risk.
1.8
1.8. Analysis
Comparison 1 Randomised controlled trials: highest versus lowest selenium exposure, Outcome 8 Non‐melanoma skin cancer risk.
1.9
1.9. Analysis
Comparison 1 Randomised controlled trials: highest versus lowest selenium exposure, Outcome 9 Lung cancer risk.
1.10
1.10. Analysis
Comparison 1 Randomised controlled trials: highest versus lowest selenium exposure, Outcome 10 Breast cancer risk.
1.11
1.11. Analysis
Comparison 1 Randomised controlled trials: highest versus lowest selenium exposure, Outcome 11 Bladder cancer risk.
1.12
1.12. Analysis
Comparison 1 Randomised controlled trials: highest versus lowest selenium exposure, Outcome 12 Prostate cancer risk.
1.13
1.13. Analysis
Comparison 1 Randomised controlled trials: highest versus lowest selenium exposure, Outcome 13 Leukaemia and lymphoma risk.
2.1
2.1. Analysis
Comparison 2 Observational studies: highest versus lowest selenium exposure, Outcome 1 Total cancer incidence and mortality.
2.2
2.2. Analysis
Comparison 2 Observational studies: highest versus lowest selenium exposure, Outcome 2 Total cancer incidence and mortality (men).
2.3
2.3. Analysis
Comparison 2 Observational studies: highest versus lowest selenium exposure, Outcome 3 Total cancer incidence and mortality (women).
2.4
2.4. Analysis
Comparison 2 Observational studies: highest versus lowest selenium exposure, Outcome 4 Total cancer incidence and mortality (ascending order of selenium levels).
2.5
2.5. Analysis
Comparison 2 Observational studies: highest versus lowest selenium exposure, Outcome 5 Total cancer incidence and mortality (ascending order of differences in selenium levels).
2.6
2.6. Analysis
Comparison 2 Observational studies: highest versus lowest selenium exposure, Outcome 6 Stomach cancer risk.
2.7
2.7. Analysis
Comparison 2 Observational studies: highest versus lowest selenium exposure, Outcome 7 Stomach cancer risk (by sex).
2.8
2.8. Analysis
Comparison 2 Observational studies: highest versus lowest selenium exposure, Outcome 8 Colorectal cancer risk.
2.9
2.9. Analysis
Comparison 2 Observational studies: highest versus lowest selenium exposure, Outcome 9 Colorectal cancer risk (by sex).
2.10
2.10. Analysis
Comparison 2 Observational studies: highest versus lowest selenium exposure, Outcome 10 Colon cancer risk.
2.11
2.11. Analysis
Comparison 2 Observational studies: highest versus lowest selenium exposure, Outcome 11 Colon cancer risk (by sex).
2.12
2.12. Analysis
Comparison 2 Observational studies: highest versus lowest selenium exposure, Outcome 12 Lung cancer incidence and mortality.
2.13
2.13. Analysis
Comparison 2 Observational studies: highest versus lowest selenium exposure, Outcome 13 Lung cancer risk (sex‐disaggregated data).
2.14
2.14. Analysis
Comparison 2 Observational studies: highest versus lowest selenium exposure, Outcome 14 Lung cancer risk (by exposure assessment).
2.15
2.15. Analysis
Comparison 2 Observational studies: highest versus lowest selenium exposure, Outcome 15 Lung cancer risk (ascending order of selenium levels).
2.16
2.16. Analysis
Comparison 2 Observational studies: highest versus lowest selenium exposure, Outcome 16 Lung cancer risk (ascending order of differences in selenium levels).
2.17
2.17. Analysis
Comparison 2 Observational studies: highest versus lowest selenium exposure, Outcome 17 Breast cancer risk (women).
2.18
2.18. Analysis
Comparison 2 Observational studies: highest versus lowest selenium exposure, Outcome 18 Bladder cancer risk.
2.19
2.19. Analysis
Comparison 2 Observational studies: highest versus lowest selenium exposure, Outcome 19 Prostate cancer risk.
2.20
2.20. Analysis
Comparison 2 Observational studies: highest versus lowest selenium exposure, Outcome 20 Prostate cancer risk (by exposure assessment).
2.21
2.21. Analysis
Comparison 2 Observational studies: highest versus lowest selenium exposure, Outcome 21 Prostate cancer risk (ascending order of selenium levels).
2.22
2.22. Analysis
Comparison 2 Observational studies: highest versus lowest selenium exposure, Outcome 22 Prostate cancer risk (ascending order of differences in selenium levels).
See this image and copyright information in PMC

Update of

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Lubinski 2011 {published data only}
    1. Lubinski J, Jaworska K, Durda K, Jakubowska A, Huzarski T, Byrski T, et al. Selenium and the risk of cancer in BRCA1 carriers. Hereditary Cancer in Clinical Practice 2011;9(Suppl 2):A5. - PMC - PubMed
Ma 2017 {published data only}
    1. Ma X, Yang Y, Li HL, Zheng W, Gao J, Zhang W, et al. Dietary trace element intake and liver cancer risk: results from two population‐based cohorts in China. International Journal of Cancer 2017;140(5):1050‐9. [PUBMED: 27859272] - PMC - PubMed
Marshall 2011 {published data only}
    1. Marshall JR, Tangen CM, Sakr WA, Wood DP Jr, Berry DL, Klein EA, et al. Phase III trial of selenium to prevent prostate cancer in men with high‐grade prostatic intraepithelial neoplasia: SWOG S9917. Cancer Prevention Research 2011;4:1761‐9. - PMC - PubMed
McNaughton 2005 {published data only}
    1. Heinen MM, Hughes MC, Ibiebele TI, Marks GC, Green AC, Pols JC. Intake of antioxidant nutrients and the risk of skin cancer. European Journal of Cancer 2007;43(18):2707‐16. - PubMed
    1. McNaughton SA, Marks GC, Gaffney P, Williams G, Green AC. Antioxidants and basal cell carcinoma of the skin: a nested case‐control study. Cancer Causes and Control 2005;16(5):609‐18. - PubMed
    1. Pols JC, Heinen MM, Hughes MC, Ibiebele TI, Marks GC, Green AC. Serum antioxidants and skin cancer risk: an 8‐year community‐based follow‐up study. Cancer Epidemiology, Biomarkers & Prevention 2009;18(4):1167‐73. - PubMed
Menkes 1986 {published data only}
    1. Batieha AM, Armenian HK, Norkus EP, Morris JS, Spate VE, Comstock GW. Serum micronutrients and the subsequent risk of cervical cancer in a population‐based nested case‐control study. Cancer Epidemiology, Biomarkers & Prevention 1993;2(4):335‐9. - PubMed
    1. Breslow RA, Alberg AJ, Helzlsouer KJ, Bush TL, Norkus EP, Morris JS, et al. Serological precursors of cancer: malignant melanoma, basal and squamous cell skin cancer, and prediagnostic levels of retinol, beta‐carotene, lycopene, alpha‐tocopherol, and selenium. Cancer Epidemiology, Biomarkers & Prevention 1995;4(8):837‐42. - PubMed
    1. Burney PG, Comstock GW, Morris JS. Serologic precursors of cancer: serum micronutrients and the subsequent risk of pancreatic cancer. American Journal of Clinical Nutrition 1989;49(5):895‐900. - PubMed
    1. Helzlsouer KJ, Alberg AJ, Norkus EP, Morris JS, Hoffman SC, Comstock GW. Prospective study of serum micronutrients and ovarian cancer. Journal of the National Cancer Institute 1996;88(1):32‐7. - PubMed
    1. Helzlsouer KJ, Comstock GW, Morris JS. Selenium, lycopene, alpha‐tocopherol, beta‐carotene, retinol, and subsequent bladder cancer. Cancer Research 1989;49(21):6144‐8. - PubMed
Michaud 2002 {published data only}
    1. Michaud DS, Hartman TJ, Taylor PR, Pietinen P, Alfthan G, Virtamo J, et al. No association between toenail selenium levels and bladder cancer risk. Cancer Epidemiology, Biomarkers & Prevention 2002;11(11):1505‐6. - PubMed
Michaud 2005 {published data only}
    1. Michaud DS, Vivo I, Morris JS, Giovannucci E. Toenail selenium concentrations and bladder cancer risk in women and men. British Journal of Cancer 2005;93(7):804‐6. - PMC - PubMed
Muka 2017 {published data only}
    1. Muka T, Kraja B, Ruiter R, Lahousse L, Keyser CE, Hofman A, et al. Dietary mineral intake and lung cancer risk: the Rotterdam Study. European Journal of Nutrition 2017;56(4):1637‐46. [PUBMED: 27073037] - PMC - PubMed
Nomura 1987 {published data only}
    1. Nomura A, Heilbrun LK, Morris JS, Stemmermann GN. Serum selenium and the risk of cancer, by specific sites: case‐control analysis of prospective data. Journal of the National Cancer Institute 1987;79(1):103‐8. - PubMed
Nomura 2000 {published data only}
    1. Nomura AMY, Lee J, Stemmermann GN, Combs GF Jr. Serum selenium and subsequent risk of prostate cancer. Cancer Epidemiology, Biomarkers & Prevention 2000;9(9):883‐7. - PubMed
NPCT 2002 {published data only}
    1. Clark L, Krongrad A, Dalkin B, Witherington R, Herlong H, Carpenter D. Decreased incidence of prostate cancer with selenium supplementation: 1983‐96 results of a double‐blind cancer prevention trial. European Journal of Cancer Prevention 1997; Vol. 6, issue 5:497‐8. - PubMed
    1. Clark LC, Combs GF Jr, Turnbull BW, Slate EH, Chalker DK, Chow J, et al. Effects of selenium supplementation for cancer prevention in patients with carcinoma of the skin: a randomized controlled trial. JAMA 1996;276(24):1957‐63. - PubMed
    1. Clark LC, Dalkin B, Krongrad A, Combs GF, Turnbull BW, Slate EH, et al. Decreased incidence of prostate cancer with selenium supplementation: results of a double‐blind cancer prevention trial. British Journal of Urology 1998;81(5):730‐4. - PubMed
    1. Clark LC, UARIZ‐CA49764 NCI‐P89‐0003. Double‐blind, randomized trial of selenium‐enriched brewer's yeast vs brewer's yeast placebo for the prevention of skin cancer in patients with a history of squamous or basal cell skin cancer (Summary Last Modified 05/91). http://www.cancer.gov. National Cancer Institute, (accessed 1 March 2004).
    1. Combs GF, Clark LC, Turnbull BW. Reduction of cancer mortality and incidence by selenium supplementation. Medizinische Klinik 1997;92(Suppl 3):42‐5. - PubMed
O'Grady 2014 {published data only}
    1. O'Grady TJ, Kitahara CM, DiRienzo AG, Gates MA. The association between selenium and other micronutrients and thyroid cancer incidence in the NIH‐AARP Diet and Health Study. PloS One 2014;9(10):e110886. [PUBMED: 25329812] - PMC - PubMed
Outzen 2016 {published data only}
    1. Outzen M, Tjonneland A, Larsen EH, Friis S, Larsen SB, Christensen J, et al. Selenium status and risk of prostate cancer in a Danish population. British Journal of Nutrition 2016;115(9):1669‐77. [PUBMED: 26971676] - PubMed
    1. Tjonneland A, Olsen A, Boll K, Stripp C, Christensen J, Engholm G, et al. Study design, exposure variables, and socioeconomic determinants of participation in Diet, Cancer and Health: a population‐based prospective cohort study of 57,053 men and women in Denmark. Scandinavian Journal of Public Health 2007;35(4):432‐41. [PUBMED: 17786808] - PubMed
Overvad 1991 {published data only}
    1. Overvad K, Wang DY, Olsen J, Allen DS, Thorling EB, Bulbrook RD, Hayward JL. Selenium in human mammary carcinogenesis: a case‐cohort study. European Journal of Cancer 1991;27(7):900‐2. - PubMed
Pantavos 2015 {published data only}
    1. Pantavos A, Ruiter R, Feskens EF, Keyser CE, Hofman A, Stricker BH, et al. Total dietary antioxidant capacity, individual antioxidant intake and breast cancer risk: the Rotterdam Study. International Journal of Cancer 2015;136(9):2178‐86. [PUBMED: 25284450] - PubMed
Park 2015 {published data only}
    1. Park SY, Haiman CA, Cheng I, Park SL, Wilkens LR, Kolonel LN, et al. Racial/ethnic differences in lifestyle‐related factors and prostate cancer risk: the Multiethnic Cohort Study. Cancer Causes & Control 2015;26(10):1507‐15. [PUBMED: 26243447] - PMC - PubMed
Peleg 1985 {published data only}
    1. Peleg I, Morris S, Hames CG. Is serum selenium a risk factor for cancer?. Medical Oncology and Tumor Pharmacotherapy 1985;2(3):157‐63. - PubMed
Peters 2007 {published data only}
    1. Peters U, Foster CB, Chatterjee N, Schatzkin A, Reding D, Andriole GL, et al. Serum selenium and risk of prostate cancer ‐ a nested case‐control study. American Journal of Clinical Nutrition 2007;85(1):209‐17. - PMC - PubMed
Peters 2008 {published data only}
    1. Asgari MM, Maruti SS, Kushi LH, White E. Antioxidant supplementation and risk of incident melanomas: results of a large prospective cohort study. Archives of Dermatology 2009;145(8):879‐82. - PMC - PubMed
    1. Peters U, Littman AJ, Kristal AR, Patterson RE, Potter JD, White E. Vitamin E and selenium supplementation and risk of prostate cancer in the vitamins and lifestyle (VITAL) study cohort. Cancer Causes Control 2008;19(1):75‐87. - PubMed
Ratnasinghe 2000 {published data only}
    1. Ratnasinghe D, Tangrea JA, Forman MR, Hartman T, Gunter EW, Qiao YL, et al. Serum tocopherols, selenium and lung cancer risk among tin miners in China. Cancer Causes and Control 2000;11(2):129‐35. - PubMed
Reid 2008 {published data only}
    1. Reid ME, Duffield‐Lillico AJ, Slate E, Natarajan N, Turnbull B, Jacobs E, et al. The nutritional prevention of cancer: 400 mcg per day selenium treatment. Nutrition and Cancer 2008;60(2):155‐63. - PubMed
Ringstad 1988 {published data only}
    1. Ringstad J, Jacobsen BK, Tretli S, Thomassen Y. Serum selenium concentration associated with risk of cancer. Journal of Clinical Pathology 1988;41(4):454‐7. - PMC - PubMed
Sakoda 2005 {published data only}
    1. Sakoda LC, Graubard BI, Evans AA, London WT, Lin WY, Shen FM, et al. Toenail selenium and risk of hepatocellular carcinoma mortality in Haimen City, China. International Journal of Cancer 2005;115(4):618‐24. - PubMed
Salonen 1984 {published data only}
    1. Salonen JT, Alfthan G, Huttunen JK, Puska P. Association between serum selenium and the risk of cancer. American Journal of Epidemiology 1984;120(3):342‐9. - PubMed
Salonen 1985 {published data only}
    1. Salonen JT, Salonen R, Lappetelainen R, Maenpaa PH, Alfthan G, Puska P. Risk of cancer in relation to serum concentrations of selenium and vitamins A and E: matched case‐control analysis of prospective data. British Medical Journal (Clinical Research Edition) 1985;290(6466):417‐20. - PMC - PubMed
SELECT 2009 {published data only}
    1. Cook ED. Selenium and Vitamin E Cancer Prevention Trial ‐ this one's for us. Journal of the National Medical Association 2002;94(9):856‐8. - PMC - PubMed
    1. Cook ED, Moody‐Thomas S, Anderson KB, Campbell R, Hamilton SJ, Harrington JM, et al. Minority recruitment to the Selenium and Vitamin E Cancer Prevention Trial (SELECT). Clinical Trials 2005;2(5):436‐42. - PubMed
    1. DeFrancesco L. Prostate cancer prevention trial launched. Nature Medicine 2001;7(10):1076. - PubMed
    1. Dunn BK, Ryan A, Ford LG. Selenium and Vitamin E Cancer Prevention Trial: a nutrient approach to prostate cancer prevention. Recent Results in Cancer Research 2009;181:183‐93. - PubMed
    1. FDA. Largest‐ever prostate cancer prevention trial. FDA Consumer 2001;35(5):8. - PubMed
Steevens 2010 {published data only}
    1. Steevens J, Brandt PA, Goldbohm RA, Schouten LJ. Selenium status and the risk of esophageal and gastric cancer subtypes: the Netherlands cohort study. Gastroenterology. 138. W.B. Saunders (Independence Square West, Philadelphia PA 19106‐3399, United States), 2010; Vol. 138, issue 5:1704‐13. - PubMed
Steinbrecher 2010 {published data only}
    1. Steinbrecher A, Meplan C, Hesketh J, Schomburg L, Endermann T, Jansen E, et al. Effects of selenium status and polymorphisms in selenoprotein genes on prostate cancer risk in a prospective study of European men. Cancer Epidemiology, Biomarkers & Prevention. 19. American Association for Cancer Research Inc. (615 Chestnut Street, 17th Floor, Philadelphia PA 19106‐3483, United States), 2010; Vol. 19, issue 11:2958‐68. - PubMed
Suadicani 2012 {published data only}
    1. Suadicani P, Hein HO, Gyntelberg F. Serum selenium level and risk of lung cancer mortality: a 16‐year follow‐up of the Copenhagen Male Study. European Respiratory Journal 2012;39(6):1443‐8. - PubMed
Sun 2016 {published data only}
    1. Sun JW, Shu XO, Li HL, Zhang W, Gao J, Zhao LG, et al. Dietary selenium intake and mortality in two population‐based cohort studies of 133 957 Chinese men and women. Public Health Nutrition 2016;19(16):2991‐8. [PUBMED: 27197889] - PMC - PubMed
Thomson 2008 {published data only}
    1. Thomson CA, Neuhouser ML, Shikany JM, Caan BJ, Monk BJ, Mossavar‐Rahmani Y, et al. The role of antioxidants and vitamin A in ovarian cancer: results from the Women's Health Initiative. Nutrition and Cancer 2008;60(6):710‐9. - PubMed
van den Brandt 1993 {published data only}
    1. Zeegers MPA, Goldbohm RA, Bode P, Brandt PA. Prediagnostic toenail selenium and risk of bladder cancer. Cancer Epidemiology, Biomarkers & Prevention 2002;11(11):1292‐7. - PubMed
    1. Brandt PA, Goldbohm RA, van't Veer P, Bode P, Dorant E, Hermus RJ, et al. A prospective cohort study on selenium status and the risk of lung cancer. Cancer Research 1993a;53(20):4860‐5. - PubMed
    1. Brandt PA, Goldbohm RA, van't Veer P, Bode P, Dorant E, Hermus RJ, et al. A prospective cohort study on toenail selenium levels and risk of gastrointestinal cancer. Journal of the National Cancer Institute 1993b;85(3):224‐9. - PubMed
    1. Brandt PA, Goldbohm RA, van't Veer P, Bode P, Dorant E, Hermus RJ, et al. Toenail selenium levels and the risk of breast cancer. American Journal of Epidemiology 1994;140(1):20‐6. - PubMed
    1. Brandt PA, Zeegers MPA, Bode P, Goldbohm RA. Toenail selenium levels and the subsequent risk of prostate cancer: a prospective cohort study. Cancer Epidemiology, Biomarkers & Prevention 2003;12(9):866‐71. - PubMed
van Noord 1987 {published data only}
    1. Noord PAH, Collette HJA, Maas MJ, Waard F. Selenium levels in nails of premenopausal breast cancer patients assessed prediagnostically in a cohort‐nested case‐referent study among women screened in the DOM project. International Journal of Epidemiology 1987;16(2):318‐22. - PubMed
Virtamo 1987 {published data only}
    1. Virtamo J, Valkeila E, Alfthan G, Punsar S, Huttunen JK, Karvonen MJ. Serum selenium and risk of cancer. A prospective follow‐up of nine years. Cancer 1987;60(2):145‐8. - PubMed
Walter 2011 {published data only}
    1. Walter RB, Brasky TM, Milano F, White E. Vitamin, mineral, and specialty supplements and risk of hematologic malignancies in the prospective VITamins And Lifestyle (VITAL) study. Cancer Epidemiology, Biomarkers & Prevention 2011;20(10):2298‐308. - PMC - PubMed
Wei 2004 {published data only}
    1. Mark SD, Qiao YL, Dawsey SM, Wu YP, Katki H, Gunter EW, et al. Prospective study of serum selenium levels and incident esophageal and gastric cancers. Journal of the National Cancer Institute 2000;92(21):1753‐63. - PubMed
    1. Wei WQ, Abnet CC, Qiao YL, Dawsey SM, Dong ZW, Sun XD, et al. Prospective study of serum selenium concentrations and esophageal and gastric cardia cancer, heart disease, stroke, and total death. American Journal of Clinical Nutrition 2004;79(1):80‐5. - PubMed
Willett 1983 {published data only}
    1. Willett WC, Polk BF, Morris JS, Stampfer MJ, Pressel S, Rosner B, et al. Prediagnostic serum selenium and risk of cancer. Lancet 1983;2(8342):130‐4. - PubMed
Yoshizawa 1998 {published data only}
    1. Yoshizawa K, Willett WC, Morris SJ, Stampfer MJ, Spiegelman D, Rimm EB, et al. Study of prediagnostic selenium level in toenails and the risk of advanced prostate cancer. Journal of the National Cancer Institute 1998;90(16):1219‐24. - PubMed
Yu 1991 {published data only}
    1. Li WG. [Preliminary observations on effect of selenium yeast on high risk populations with primary liver cancer]. Zhonghua Yu Fang Yi Xue Za Zhi [Chinese Journal of Preventive Medicine] 1992;26(5):268‐71. - PubMed
    1. Yu S, Li W, Zhu Y. Chemoprevention of liver cancer. CCPC‐93: Second International Cancer Chemo Prevention Conference; 1993 April 28‐30; Berlin (Meeting Abstracts)..
    1. Yu SY, Zhu YJ, Li WG, Huang QS, Huang CZ, Zhang QN, et al. A preliminary report on the intervention trials of primary liver cancer in high‐risk populations with nutritional supplementation of selenium in China. Biological Trace Element Research 1991;29(3):289‐94. - PubMed
Yu 1997 {published data only}
    1. Li WG. [Preliminary observations on effect of selenium yeast on high risk populations with primary liver cancer]. Zhonghua Yu Fang Yi Xue Za Zhi [Chinese Journal of Preventive Medicine] 1992;26(5):268‐71. - PubMed
    1. Yu SY, Zhu YJ, Li WG. Protective role of selenium against hepatitis B virus and primary liver cancer in Qidong. Biological Trace Element Research 1997;56(1):117‐24. [MEDLINE: ] - PubMed
    1. Yu SY, Zhu YJ, Li WG, Huang QS, Huang CZ, Zhang QN, et al. A preliminary report on the intervention trials of primary liver cancer in high‐risk populations with nutritional supplementation of selenium in China. Biological Trace Element Research 1991;29(3):289‐94. - PubMed
Yu 1999 {published data only}
    1. Yu MW, Horng IS, Hsu KH, Chiang YC, Liaw YF, Chen CJ. Plasma selenium levels and risk of hepatocellular carcinoma among men with chronic hepatitis virus infection. American Journal of Epidemiology 1999;150(4):367‐74. - PubMed

References to studies excluded from this review

Albanes 2014 {published data only}
    1. Albanes D, Till C, Klein EA, Goodman PJ, Mondul AM, Weinstein SJ, et al. Plasma tocopherols and risk of prostate cancer in the Selenium and Vitamin E Cancer Prevention Trial (SELECT). Cancer Prevention Research (Philadelphia, Pa.) 2014;7(9):886‐95. [PUBMED: 24961880] - PMC - PubMed
Bates 2011 {published data only}
    1. Bates CJ, Hamer M, Mishra GD. Redox‐modulatory vitamins and minerals that prospectively predict mortality in older British people: the National Diet and Nutrition Survey of people aged 65 years and over. British Journal of Nutrition 2011;105(1):123‐32. [EPI_EU_Bates 2011] - PMC - PubMed
Bostick 1993 {published data only}
    1. Bostick RM, Potter JD, McKenzie DR, Sellers TA, Kushi LH, Steinmetz KA, et al. Reduced risk of colon cancer with high intake of vitamin E: the Iowa Women's Health Study. Cancer Research 1993;53(18):4230‐7. - PubMed
Brock 1991 {published data only}
    1. Brock KE, Gridley G, Morris JS, Willett WC. Serum selenium level in relation to in situ cervical cancer in Australia. Journal of the National Cancer Institute 1991;83(4):292‐3. - PubMed
Chen 1988 {published data only}
    1. Chen Q. [Protective effects of selenium, zinc and copper on lung cancer]. Zhonghua Yu Fang Yi Xue Za Zhi [Chinese Journal of Preventive Medicine] 1988;22(4):221‐4. - PubMed
Chen 2003 {published data only}
    1. Chen K, Qiu JL, Sui LM, Yu WP, Wang JY, Zhang LJ. Nutrient intake and gastric cancer in residents of Zhoushan Islands, China. Digestive and Liver Disease 2003;35(12):912‐3. - PubMed
Connelly‐Frost 2009 {published data only}
    1. Connelly‐Frost A, Poole C, Satia JA, Kupper LL, Millikan RC, Sandler RS. Selenium, folate, and colon cancer. Nutrition and Cancer 2009;61(2):165‐78. - PMC - PubMed
Costello 2001 {published data only}
    1. Costello AJ. A randomized, controlled chemoprevention trial of selenium in familial prostate cancer: rationale, recruitment, and design issues. Urology 2001;57(4 Suppl 1):182‐4. - PubMed
Criqui 1991 {published data only}
    1. Criqui MH, Bangdiwala S, Goodman DS, Blaner WS, Morris JS, Kritchevsky S, et al. Selenium, retinol, retinol‐binding protein, and uric acid. Associations with cancer mortality in a population‐based prospective case‐control study. Annals of Epidemiology 1991;1(5):385‐93. - PubMed
Cui 2007 {published data only}
    1. Cui Y, Vogt S, Olson N, Glass AG, Rohan TE. Levels of zinc, selenium, calcium, and iron in benign breast tissue and risk of subsequent breast cancer. Cancer Epidemiology, Biomarkers & Prevention 2007;16(8):1682‐5. - PubMed
Davies 2002 {published data only}
    1. Davies TW, Treasure FP, Welch AA, Day NE. Diet and basal cell skin cancer: results from the EPIC‐Norfolk cohort. British Journal of Dermatology 2002;146(6):1017‐22. - PubMed
Epplein 2014 {published data only}
    1. Epplein M, Burk RF, Cai Q, Hargreaves MK, Blot WJ. A prospective study of plasma Selenoprotein P and lung cancer risk among low‐income adults. Cancer Epidemiology, Biomarkers & Prevention 2014;23(7):1238‐44. - PMC - PubMed
Fleshner 2003 {published data only}
    1. Fleshner N, CAN‐CNIC‐PRP1. Phase II randomized study of vitamin E, selenium, and soy protein isolate in patients with high‐grade prostatic intraepithelial neoplasia. http://www.cancer.gov (accessed 1 April 2004).
Geybels 2013 {published data only}
    1. Geybels MS, Verhage BA, Schooten FJ, Goldbohm RA, Brandt PA. Advanced prostate cancer risk in relation to toenail selenium levels. Journal of the National Cancer Institute 2013;105(18):1394‐401. [PUBMED: 23878355] - PubMed
Geybels 2014 {published data only}
    1. Geybels MS, Brandt PA, Schouten LJ, Schooten FJ, Breda SG, Rayman MP, et al. Selenoprotein gene variants, toenail selenium levels, and risk for advanced prostate cancer. Journal of the National Cancer Institute 2014;106(3):dju003. [PUBMED: 24563517] - PubMed
Hagmar 1992 {published data only}
    1. Hagmar L, Linden K, Nilsson A, Norrving B, Akesson B, Schutz A, et al. Cancer incidence and mortality among Swedish Baltic Sea fishermen. Scandinavian Journal of Work, Environment and Health 1992;18(4):217‐24. - PubMed
Harris 2012 {published data only}
    1. Harris Holly R, Brgkvist L, Wolk A. Selenium intake and breast cancer mortality in a cohort of Swedish women. Breast Cancer Research and Treatment 2012;134(3):1269‐77. - PubMed
Hartman 2002 {published data only}
    1. Hartman TJ, Taylor PR, Alfthan G, Fagerstrom R, Virtamo J, Mark SD, et al. Toenail selenium concentration and lung cancer in male smokers (Finland). Cancer Causes & Control 2002;13(10):923‐8. - PubMed
Huzarski 2006 {published data only}
    1. Huzarski T, Byrski T, Gronwald J, Kowalska E, Zajaczek S, Gorski B, et al. A lowering of breast and ovarian cancer risk in women with a BRCA1 mutation by selenium supplementation of diet. Hereditary Cancer in Clinical Practice 2006;4(1):58. - PMC - PubMed
Joniau 2007 {published data only}
    1. Joniau S, Goeman L, Roskams T, Lerut E, Oyen R, Van PH. Effect of nutritional supplement challenge in patients with isolated high‐grade prostatic intraepithelial neoplasia. Urology 2007;69(6):1102‐6. - PubMed
Karunasinghe 2012 {published data only}
    1. Karunasinghe N, Han DY, Goudie M, Zhu S, Bishop K, Wang A, et al. Prostate disease risk factors among a New Zealand cohort. Journal of Nutrigenetics and Nutrigenomics 2012;5(6):339‐51. [PUBMED: 23363810] - PubMed
Kellen 2008 {published data only}
    1. Kellen E, Zeegers MP, Bruckers L, Buntinx F. The investigation of a geographical cluster of bladder cancer. Acta Clinica Belgica 2008;63(5):313‐20. - PubMed
Kilander 2001 {published data only}
    1. Kilander L, Berglund L, Boberg M, Vessby B, Lithell H. Education, lifestyle factors and mortality from cardiovascular disease and cancer. A 25‐year follow‐up of Swedish 50‐year‐old men. International Journal of Epidemiology 2001;30(5):1119‐26. - PubMed
Knekt 1988a {published data only}
    1. Knekt P, Reunanen A, Aromaa A, Heliovaara M, Hakulinen T, Hakama M. Serum cholesterol and risk of cancer in a cohort of 39,000 men and women. Journal of Clinical Epidemiology 1988;41(6):519‐30. - PubMed
Knekt 1988b {published data only}
    1. Knekt P, Aromaa A, Maatela J, Aaran RK, Nikkari T, Hakama M, et al. Serum vitamin E and risk of cancer among Finnish men during a 10‐year follow‐up. American Journal of Epidemiology 1988;127(1):28‐41. - PubMed
Knekt 1991 {published data only}
    1. Knekt P, Aromaa A, Maatela J, Alfthan G, Aaran RK, Nikkari T, et al. Serum micronutrients and risk of cancers of low incidence in Finland. American Journal of Epidemiology 1991;134(4):356‐61. - PubMed
Kok 1987b {published data only}
    1. Kok FJ, Duijn CM, Hofman A, Vermeeren R, Bruijn AM, Valkenburg HA. Micronutrients and the risk of lung cancer (letter). New England Journal of Medicine 1987c;316:1416. - PubMed
Kune 2006 {published data only}
    1. Kune G, Watson L. Colorectal cancer protective effects and the dietary micronutrients folate, methionine, vitamins B6, B12, C, E, selenium, and lycopene. Nutrition and Cancer 2006;56(1):11‐21. - PubMed
Kuroda 1988 {published data only}
    1. Kuroda M, Imura T, Morikawa K, Hasegawa T. Decreased serum levels of selenium and glutathione peroxidase activity associated with aging, malignancy and chronic hemodialysis. Trace Elements in Medicine 1988;5(3):97‐103.
Lane 2017 {published data only}
    1. Lane JA, Oliver SE, Appleby PN, Lentjes MA, Emmett P, Kuh D, et al. Prostate cancer risk related to foods, food groups, macronutrients and micronutrients derived from the UK Dietary Cohort Consortium food diaries. European Journal of Clinical Nutrition 2017;71(2):274‐83. [PUBMED: 27677361] - PMC - PubMed
Lawson 2007 {published data only}
    1. Lawson KA, Wright ME, Subar A, Mouw T, Hollenbeck A, Schatzkin A, et al. Multivitamin use and risk of prostate cancer in the National Institutes of Health‐AARP Diet and Health Study. Journal of the National Cancer Institute 2007;99(10):754‐64. - PubMed
Le Marchand 2006 {published data only}
    1. Marchand L, Saltzman BS, Hankin JH, Wilkens LR, Franke AA, Morris SJ, et al. Sun exposure, diet, and melanoma in Hawaii Caucasians. American Journal of Epidemiology 2006;164(3):232‐45. - PubMed
Li 2004b {published data only}
    1. Li H, Li HQ, Wang Y, Xu HX, Fan WT, Wang ML, et al. An intervention study to prevent gastric cancer by micro‐selenium and large dose of allitridum. Chinese Medical Journal 2004;117(8):1155‐60. - PubMed
Limburg 2005 {published data only}
    1. Limburg PJ, Wei W, Ahnen DJ, Qiao Y, Hawk ET, Wang G, et al. Randomized, placebo‐controlled, esophageal squamous cell cancer chemoprevention trial of selenomethionine and celecoxib. Gastroenterology 2005;129(3):863‐73. - PubMed
Linxian Pilot 2000 {published data only}
    1. NCI‐OH95‐C‐N026NCI‐P00‐0157. Pilot randomized chemoprevention study of selenium and celecoxib, alone or in combination, in patients with esophageal squamous dysplasia who are residing in Linxian, People's Republic of China. http://www.cancer.gov/search/ViewClinicalTrials.aspx?cdrid=67930&ver... (accessed 25 February 2009).
Loeb 2015 {published data only}
    1. Loeb S, Peskoe SB, Joshu CE, Huang WY, Hayes RB, Carter HB, et al. Do environmental factors modify the genetic risk of prostate cancer?. Cancer Epidemiology, Biomarkers & Prevention 2015;24(1):213‐20. [PUBMED: 25342390] - PMC - PubMed
Martinez 2014 {published data only}
    1. Martinez EE, Darke AK, Tangen CM, Goodman PJ, Fowke JH, Klein EA, et al. A functional variant in NKX3.1 associated with prostate cancer risk in the Selenium and Vitamin E Cancer Prevention Trial (SELECT). Cancer Prevention Research 2014;7(9):950‐7. [PUBMED: 24894197] - PMC - PubMed
Neuhouser 2009 {published data only}
    1. Neuhouser ML, Wassertheil‐Smoller S, Tomson C, Aragaki A, Anderson GL, Manson JE, et al. Multivitamin use and risk of cancer and cardiovascular disease in the women's health initiative cohorts. Archives of Internal Medicine 2009;169(3):294‐304. - PMC - PubMed
Persson 2000 {published data only}
    1. Persson‐Moschos ME, Stavenow L, Akesson B, Lindgarde F. Selenoprotein P in plasma in relation to cancer morbidity in middle‐aged Swedish men. Nutrition and Cancer 2000;36(1):19‐26. - PubMed
Ray 2006 {published data only}
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Rayman 2001 {published data only}
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