Toenail Selenium Research Articles

Determination of selenium status using the nail biologic monitor in a canine model

Toenails and fingernails are routinely used to estimate selenium status in epidemiological studies; however, literature validating nail selenium concentration as a surrogate for critical organs is limited. In this study diets of intact male dogs were selenium supplemented at two physiological levels (3 and 6 μg/kg/day) in two different forms, selenomethionine and selenium-enriched bioformed yeast. The selenium-adequate basal diet consumed by the treatment and control groups during the 4-week run-in period and throughout the trial contained 0.3 ppm selenium. After 7 months the dogs in the two treatment groups and the control group were euthanized. Representative tissue samples from prostate, brain, liver, heart and skeletal muscle were collected, rinsed and frozen. Toenail clippings from multiple toes were also collected. Selenium was determined by neutron activation analysis using Se77m (half life = 17.4 s) at the University of Missouri Research Reactor Center. NIST SRM 1577, Bovine Liver was analyzed as a quality control. The analysts were blinded to control and treatment group assignments. As expected, tissue selenium levels increased proportionally with supplementation. A slightly greater increase in tissue selenium was observed for the purified selenomethionine compared to the bioformed yeast; however this trend was significant only for brain tissue. Toenail selenium concentrations and tissue selenium were highly correlated (p < 0.003) with Pearson coefficients of 0.759 (skeletal muscle), 0.745 (heart), 0.729 (brain), 0.723 (prostate), and 0.632 (liver). The toenail biologic monitor accurately assesses selenium status in skeletal muscle, heart, brain, prostate, and liver in the canine model.

Mercury exposure and risk of cardiovascular disease in two U.S. cohorts.

Exposure to methylmercury from fish consumption has been linked to a potentially increased risk of cardiovascular disease, but evidence from prior studies is equivocal. Beneficial effects of the ingestion of fish and selenium may also modify such effects. Among subjects from two U.S. cohorts (a total of 51,529 men and 121,700 women) whose toenail clippings had been stored, we prospectively identified incident cases of cardiovascular disease (coronary heart disease and stroke) in 3427 participants and matched them to risk-set-sampled controls according to age, sex, race, and smoking status. Toenail mercury and selenium concentrations were assessed with the use of neutron-activation analysis. Other demographic characteristics, cardiovascular risk factors, fish consumption, and lifestyle habits were assessed by means of validated questionnaires. Associations between mercury exposure and incident cardiovascular disease were evaluated with the use of conditional logistic regression. Median toenail mercury concentrations were 0.23 μg per gram (interdecile range, 0.06 to 0.94) in the case participants and 0.25 μg per gram (interdecile range, 0.07 to 0.97) in the controls. In multivariate analyses, participants with higher mercury exposures did not have a higher risk of cardiovascular disease. For comparisons of the fifth quintile of mercury exposure with the first quintile, the relative risks were as follows: coronary heart disease, 0.85 (95% confidence interval [CI], 0.69 to 1.04; P=0.10 for trend); stroke, 0.84 (95% CI, 0.62 to 1.14; P=0.27 for trend); and total cardiovascular disease, 0.85 (95% CI, 0.72 to 1.01; P=0.06 for trend). Findings were similar in analyses of participants with low selenium concentrations or low overall fish consumption and in several additional sensitivity analyses. We found no evidence of any clinically relevant adverse effects of mercury exposure on coronary heart disease, stroke, or total cardiovascular disease in U.S. adults at the exposure levels seen in this study. (Funded by the National Institutes of Health.).

Distribution of toenail selenium levels in young adult Caucasians and African Americans in the United States: The CARDIA Trace Element Study

Background Data on selenium (Se) levels in American young adults, especially in African Americans, are lacking. Objective This study presented toenail Se distributions in American young adults of both genders, including both Caucasians and African Americans; and explored potential predictors of toenail Se levels. Data and methods Data from the Coronary Artery Risk Development in Young Adults study among 4252 American young adults, aged 20–32 in 1987 was used to examine toenail Se levels by instrumental neutron-activation analysis. The distribution of Se levels was described and multivariable linear regression was used to examine potential modifiers of toenail Se concentration within ethnicity–gender subgroups. Results The geometric mean of toenail Se in this cohort was 0.844 μg/g (95% CI, 0.840–0.849 μg/g) and the median was 0.837 μg/g (95% CI, 0.833–0.844 μg/g). Median levels from lowest to highest quintile were 0.691, 0.774, 0.838, 0.913 and 1.037 μg/g. Se levels varied geographically, and were generally in accordance with its concentrations in local soil. Males, African Americans, current smokers, heavy drinkers and less educated participants were more likely to have low Se levels. Conclusion This study suggests that toenail Se levels vary geographically depending on soil Se concentrations. In addition to gender, ethnicity and education level, smoking status and alcohol consumption are two important indicators of Se status since they are modifiable lifestyle factors. Findings from this study might aid public health professionals in identifying people at relatively high or low Se levels, so that chronic disease prevention efforts can be directed toward these subgroups.

Demographic and lifestyle factors and selenium levels in men and women in the U.S.

Selenium is an antioxidant trace element linked to cardiovascular disease and cancer. Although diet is a major source, relatively little else is known about independent determinants of selenium levels in free-living humans. In this study, we aimed to investigate the independent demographic, lifestyle, and dietary determinants of selenium levels in 1,997 men and 1,905 women in two large prospective U.S. cohorts. Toenail selenium levels were quantified using neutron activation analysis. Diet, geographic residence, demographic, and environmental factors were assessed by validated self-administered questionnaires. Multivariate generalized linear models were conducted to assess the independent relations of these factors with toenail selenium levels, correcting for measurement error in the diet. In multivariable-adjusted analyses, independent predictors of higher selenium were male gender (6.3% higher levels); living in West and Northern-Midwest U.S. regions (8.9% and 7.4% higher than Southern-Midwest regions, respectively); consumption of beef and bread products (between 0.7 - 2.5% higher per daily serving); and selenium supplement use (6.9% higher than non-users); whereas cigarette smoking (5-10% lower than never smokers) , older age (0.6% lower per 5 years), and consumption of eggs, white rice, dairy products, coffee, and alcohol (between 0.1 to 2.0% lower per daily serving) were associated with lower selenium. Multiple dietary and non-dietary factors independently predicted selenium levels, suggesting that both consumption and non-dietary processes (e.g., related to oxidant status) may affect levels. Significant geographic variation in selenium levels exists in the US.

Distribution of toenail selenium levels in young adult Caucasians and African Americans in the United States: The CARDIA Trace Element Study

Distribution of toenail selenium levels in young adult Caucasians and African Americans in the United States: The CARDIA Trace Element Study

Toenail selenium status and the risk of Barrett’s esophagus: the Netherlands Cohort Study

ObjectiveTo investigate the association between selenium and the risk of Barrett’s esophagus (BE), the precursor lesion of esophageal adenocarcinoma.MethodsData from the prospective Netherlands Cohort Study were used. This cohort study was initiated in 1986, when 120,852 subjects aged 55–69 years completed a questionnaire on dietary habits and lifestyle, and provided toenail clippings for the determination of baseline selenium status. After 16.3 years of follow-up, 253 BE cases (identified through linkage with the nationwide Dutch pathology registry) and 2,039 subcohort members were available for case–cohort analysis. Cox proportional hazards models were used to calculate incidence rate ratios (RR).ResultsThe multivariable-adjusted RR for the highest versus the lowest quartile of toenail selenium was 1.06 (95% CI 0.71–1.57). No dose–response trend was seen (p trend = 0.99). No association was found in subgroups defined by sex, smoking status, body mass index (BMI), or intake of antioxidants. For BE cases that later progressed to high-grade dysplasia or adenocarcinoma, the RR for a selenium level above the median vs. below the median was 0.64 (95% CI 0.24–1.76).ConclusionsIn this large prospective cohort study, we found no evidence of an association between selenium and risk of BE.Electronic supplementary materialThe online version of this article (doi:10.1007/s10552-010-9651-1) contains supplementary material, which is available to authorized users.

Associations of Toenail Selenium Levels With Inflammatory Biomarkers of Fibrinogen, High-Sensitivity C-Reactive Protein, and Interleukin-6: The CARDIA Trace Element Study

The authors examined the associations of toenail selenium levels with blood concentrations of fibrinogen, high-sensitivity C-reactive protein (hs-CRP), and interleukin-6 (IL-6) in an 18-year follow-up study comprising 4,032 Americans aged 20-32 years at baseline (1987) from the Coronary Artery Risk Development in Young Adults (CARDIA) Trace Element Study. Toenail samples were collected in 1987, and selenium concentrations were measured by means of instrumental neutron-activation analysis. Fibrinogen level was analyzed in 1990, 1992, and 2005; hs-CRP was assessed in 1992, 2000, and 2005; and IL-6 was measured in 2005. After adjustment for potential confounders, no statistically significant associations between toenail selenium levels and any of the 3 inflammatory biomarkers were documented. Comparing the highest quintile of toenail selenium level with the lowest, odds ratios for elevated levels of fibrinogen (>460 mg/mL), hs-CRP (>3 microg/mL), and IL-6 (>3.395 pg/mL, 80th percentile) were 1.03 (95% confidence interval (CI): 0.77, 1.38; P for trend = 0.76), 1.02 (95% CI: 0.83, 1.27; P for trend = 0.92), and 0.98 (95% CI: 0.71, 1.36; P for trend = 0.82), respectively. Gender, race/ethnicity, smoking status, and selenium supplementation did not appreciably modify these results. This study found no associations between toenail selenium and inflammation as measured by fibrinogen, hs-CRP, and IL-6.

Self-organizing maps classification of epidemiological data and toenail selenium content monitored on cancer and healthy patients from Poland

This paper deals with epidemiological multivariate statistical analysis of cancer and health patients from Pomeranian and Lubuskie Voivodships, Poland. The anthropometric and epidemiologic data include 8 parameters: toenail selenium concentration, sex, age, body mass index (BMI), smoking status, taking of Se supplements, health state, and family history of cancer. The self-organizing maps (SOM) are used for simultaneous classification of parameters and patients with relation to cancer diagnosis. Three different patterns (groups) of patients with cancer diagnosis are outlined: (i) older, smoking men with low toenail selenium concentration; (ii) older smoking women with family relation to cancer and toenail selenium deficiency; (iii) middle, aged nonsmokers with high level of selenium toenail concentration. The simultaneous classification of parameters and patients makes it possible to determine discriminating parameters for each pattern and relations between parameters. The relation of each parameter to cancer disease is discussed as special attention is paid to toenail selenium deficiency. More than 80% of patients with cancer diagnosis possess toenail selenium deficiency, accompanied by old age and smoking.

Longitudinal association between toenail selenium levels and measures of subclinical atherosclerosis: The CARDIA trace element study

ObjectivesTo examine the longitudinal association between toenail selenium levels and subclinical atherosclerosis over an 18-year period. MethodsToenail selenium concentrations were examined among 3112 Americans age 20–32 years in 1987 and measured by instrumental neutron-activation analysis. Subclinical atherosclerosis, including common, bulb and internal carotid intima–media thickness (CIMT), was measured in 2005 and coronary artery calcium (CAC) score in 2000 and 2005. General linear regression was developed examining the relation between toenail selenium levels and CIMTs, and logistic regression for repeated outcomes was employed estimating the risk of having CAC>0. ResultsAfter adjustment for potential confounders, no associations were observed between toenail selenium levels and CIMTs as well as CAC score. Comparing participants in the highest with the lowest quintile of selenium, the CIMT was 0.005mm (SE=0.008mm, Ptrend=0.39), 0.018mm (SE=0.019mm, Ptrend=0.49), and 0.017mm (SE=0.014mm, Ptrend=0.21) thicker measured in common, bulb and internal carotid, respectively. The adjusted odds ratio of having CAC>0 was 0.95 (95% CI: 0.67–1.35; Ptrend=0.999). ConclusionsNo associations were observed between toenail selenium and measures of subclinical atherosclerosis among American young adults. This study does not support an atherosclerotic mechanism of selenium for risk reduction of cardiovascular disease.

Toenail selenium status and DNA repair capacity among female BRCA1 mutation carriers

Selenium is an important cofactor of various antioxidant enzymes and has been shown to enhance DNA repair in normal human fibroblasts. Oral selenium supplementation has also been shown to decrease the number of chromosome breaks in BRCA1 mutation carriers. Because the predisposition to cancer among BRCA1 mutation carriers may be linked to high rates of DNA damage and chromosome breakage, we evaluated the association between toenail selenium concentrations and three measures of DNA repair capacity (the single-cell alkaline gel electrophoresis (comet) assay, the micronucleus test, and the enumeration of gamma-H2AX nuclear foci) in female BRCA1 mutation carriers and in non-carriers. Toenail selenium levels were inversely associated with levels of chromosomal damage following exposure to gamma-irradiation, as assessed by the micronucleus test. This association was limited to women with a BRCA1 mutation (p = 0.03). Toenail selenium was not a significant predictor of DNA repair capacity, as quantified by either the comet assay or the number of gamma-H2AX foci, in carriers or in non-carriers. These results provide evidence for a possible protective effect of selenium against BRCA1-associated breast cancers.

Abstract A113: Toenail selenium and the risk of esophageal and gastric cancer subtypes: The Netherlands Cohort Study

Abstract Purpose: Selenium may protect against the development of esophageal squamous cell carcinoma (ESCC), esophageal adenocarcinoma (EAC) and gastric cardia adenocarcinoma (GCA). Only in very few studies have the associations with ESCC and GCA been investigated, and no epidemiologic studies exist on EAC. Methods: We studied the association between selenium and risk of ESCC, EAC, and GCA within the prospective Netherlands Cohort Study, conducted among 120,852 men and women aged 55–69 years at baseline. In September 1986, the cohort members completed a questionnaire on risk factors for cancer and provided toenail clippings for determination of baseline selenium status. After 16.3 years of follow-up, 64 ESCC, 112 EAC, and 114 GCA cases and 2072 subcohort members with toenail selenium data were available for case-cohort analysis. Incidence rate ratios (RR) were calculated using Cox proportional hazards models. Results: In multivariable analyses of selenium status, we found an inverse association with ESCC (RR quartile 4 versus quartile 1 0.37, 95% confidence intervals (CI) 0.16–0.86), and a borderline significant inverse association with GCA (RR 0.52, 95% CI 0.27–1.02). No overall association was observed for EAC (RR 0.76, 95% CI 0.41–1.40), although results suggested an inverse association in women. Stratified analyses showed stronger associations in never smokers, and (only for EAC) in subjects with a low antioxidant intake. Conclusions: This prospective study supports an inverse association between toenail selenium and risk of ESCC and GCA and suggests an inverse association with risk of EAC in subgroups (women, never smokers, and low antioxidant consumers). These associations need confirmation. Citation Information: Cancer Prev Res 2010;3(1 Suppl):A113.

Selenium Status and the Risk of Esophageal and Gastric Cancer Subtypes: The Netherlands Cohort Study

Selenium may protect against the development of esophageal squamous cell carcinoma (ESCC), esophageal adenocarcinoma (EAC), and gastric cardia adenocarcinoma (GCA). Only in very few studies have the associations with ESCC and GCA been investigated, and no epidemiologic studies exist on EAC. We studied the association between selenium and risk of ESCC, EAC, and GCA within the prospective Netherlands Cohort Study, conducted among 120,852 men and women aged 55-69 years at baseline. In September 1986, the cohort members completed a questionnaire on risk factors for cancer and provided toenail clippings for determination of baseline selenium status. After 16.3 years of follow-up, 64 ESCC, 112 EAC, and 114 GCA cases and 2072 subcohort members were available for case-cohort analysis. Incidence rate ratios (RR) were calculated using Cox proportional hazards models. In multivariable analyses of selenium status, we found an inverse association with ESCC (RR(per standard unit increment), 0.80; 95% confidence interval [CI]: 0.67-0.96) and a borderline significant inverse association with GCA (RR, 0.91; 95% CI: 0.80-1.02). No overall association was observed for EAC (RR, 1.05; 95% CI: 0.95-1.15), but, for women and never smokers, significant inverse associations were found (RR(per standard unit increment), 0.72; 95% CI: 0.61-0.84 and RR(per standard unit increment), 0.74; 95% CI: 0.64-0.86, respectively). This prospective study supports an inverse association between toenail selenium and risk of ESCC and GCA and suggests an inverse association with risk of EAC in subgroups (women, never smokers, and low antioxidant consumers). These associations need confirmation.

Lung cancer in a U.S. population with low to moderate arsenic exposure.

BackgroundLittle is known about the carcinogenic potential of arsenic in areas with low to moderate concentrations of arsenic (< 100 μg/L) in drinking water.ObjectivesWe examined associations between arsenic and lung cancer.MethodsA population-based case–control study of primary incident lung cancer was conducted in 10 counties in two U.S. states, New Hampshire and Vermont. The study included 223 lung cancer cases and 238 controls, each of whom provided toenail clippings for arsenic exposure measurement by inductively coupled–plasma mass spectrometry. We estimated odds ratios (ORs) of the association between arsenic exposure and lung cancer using unconditional logistic regression with adjustment for potential confounders (age, sex, race/ethnicity, smoking pack-years, education, body mass index, fish servings per week, and toenail selenium level).ResultsArsenic exposure was associated with small-cell and squamous-cell carcinoma of the lung [OR = 2.75; 95% confidence interval (CI), 1.00–7.57] for toenail arsenic concentration ≥ 0.114 μg/g, versus < 0.05 μg/g. A history of lung disease (bronchitis, chronic obstructive pulmonary disease, or fibrosis) was positively associated with lung cancer (OR = 2.86; 95% CI, 1.39–5.91). We also observed an elevated risk of lung cancer among participants with a history of lung disease and toenail arsenic ≥ 0.05 μg/g (OR = 4.78; 95% CI, 1.87–12.2) than among individuals with low toenail arsenic and no history of lung disease.ConclusionAlthough this study supports the possibility of an increased risk of specific lung cancer histologic types at lower levels of arsenic exposure, we recommend large-scale population-based studies.

Methods of assessment of selenium status in humans: a systematic review

Background: To understand the effect of selenium intake on health, it is important to identify sensitive and population-specific biomarkers of selenium status.Objective: The objective of this systematic review was to assess the usefulness of biomarkers of selenium status in humans.Design: The methods included a structured search strategy on Ovid MEDLINE, EMBASE (Ovid), and Cochrane databases; formal inclusion and exclusion criteria; data extraction into an Access database; validity assessment; and meta-analysis.Results: The data from 18 selenium supplementation studies (of which 9 were randomized controlled trials and 1 was considered to be at low risk of bias) indicate that plasma, erythrocyte, and whole-blood selenium, plasma selenoprotein P, and plasma, platelet, and whole-blood glutathione peroxidase activity respond to changes in selenium intake. Although there is a substantial body of data for plasma selenium, more large, high-quality, randomized controlled trials are needed for this biomarker, as well as for the other biomarkers, to explore the reasons for heterogeneity in response to selenium supplementation. There was insufficient evidence to assess the usefulness of other potential biomarkers of selenium status, including urinary selenium, plasma triiodothyroxine:thyroxine ratio, plasma thyroxine, plasma total homocysteine, hair and toenail selenium, erythrocyte, and muscle glutathione peroxidase activity.Conclusions: For all potentially useful biomarkers, more information is needed to evaluate their strengths and limitations in different population groups, including the effects of varying intakes, the duration of intervention, baseline selenium status, and possible confounding effects of genotype.

Toenail selenium level among healthy residents of two Polish Districts

The goal of this study was to evaluate the selenium mass fraction in toenail clippings taken from random inhabitants living in various areas of the Pomeranian (Northern Poland) and Lubuskie (Western Poland) Districts. Toenail clippings were analyzed by instrumental neutron activation analysis (INAA) giving means of 0.57±0.10 and 0.60±0.16 mg·kg−1 for the two areas, respectively, but the difference was statistically not significant. In additional, it was found that gender, age, body mass index (BMI), smoking, and selenium supplementation are factors with apparent effects to the selenium levels in toenail clippings.

Selenium and Risk of Bladder Cancer: A Population-Based Case-Control Study

Emerging evidence indicates a potential role of selenium in the prevention of several types of cancer, including bladder cancer. We investigated the association between toenail selenium concentrations and bladder cancer risk in a population-based case-control study in New Hampshire. We analyzed data from 857 incidence cases diagnosed between July 1, 1994 and June 30, 2001 and 1,191 general population controls. Newly diagnosed cases of bladder cancer were identified from the New Hampshire State Cancer Registry, which operates a rapid reporting system. Controls were selected from population lists (driver's license and Medicare enrollment). We used logistic regression analyses to generate odds ratios (OR) and 95% confidence intervals (95% CI), controlling for age, sex, and pack-years of smoking and conducted separate analyses according to the intensity of p53 immunohistochemical staining of the tumor. Overall, toenail selenium concentrations were not significantly related to bladder cancer [OR Q4 versus Q1, 0.90 (95% CI, 0.68-1.19); P(trend) = 0.15]. However, within specific subgroups there were inverse associations, i.e., among moderate smokers [OR, 0.61 (95% CI, 0.39-0.96); P(trend) = 0.004], women [OR, 0.66 (95% CI, 0.40-1.10); P(trend) = 0.11], and those with p53-positive cancers [OR Q4 versus Q1, 0.57 (95% CI, 0.34-0.94); P(trend) = 0.01]. Our results indicate that selenium is not inversely related to risk of bladder cancer overall; however, they raise the possibility that selenium may be preventive in certain molecular phenotypes of tumors (e.g., p53 positive) or within certain subsets of a population (e.g., women or moderate smokers).

Toenail selenium levels and gastric cancer risk in Cali, Colombia

To examine an association between selenium level and gastric cancer (GC) risk, a hospital-based case-control study was conducted in Cali, Colombia. Selenium concentrations in toenails were compared between 142 GC patients and 244 controls selected from hospitalized non-cancer patients. GC risk was lowest in the lowest quartile of selenium level and highest in the second highest quartile (age-, sex-, hospital-, and sampling-season-adjusted odds ratio [OR]: 5.9, 95% confidence interval: 2.8, 12.4). This association was not modified by either tumor location or Lauren's histological type. The magnitude of ORs was not affected by other diets that were significantly associated with GC risk. Since selenium levels were relatively high in cases and in controls, our results indicate that an inverse association between selenium level and GC risk may exist only among populations with low selenium levels.

Selenium and zinc in hair and toenails in relation to the physical and mental health status of older adults: The Freemasons Health study in New Zealand

Objectives: To determine the associations of selenium and zinc on health. Methods: A cross‐sectional study; adults (mean age 65 years), Freemasons or spouses resident of the North Island of New Zealand; measures of cognition, the Timed Up and Go (TUG) test, and hair and toenail zinc and selenium levels. Multivariable logistic regression was used to determine significant associations. Results: Univariate analyses showed a significant association of decreased likelihood of impaired performance (&gt; 9.5 seconds) on the TUG test with increasing quartiles of nail selenium (odds ratio 0.73; 95% confidence interval 0.61–0.87). The association persisted in a multivariate model. No associations were seen for any of the other measures. Conclusion: Low nail selenium levels were associated with impaired physical function, as a result of chance from multiplicity problems, bias or a true adverse effect of selenium deficiency. Prospective studies are necessary to more reliably discern temporal associations of micronutrients on health.

Noninvasive Prediction of Prostatic DNA Damage by Oxidative Stress Challenge of Peripheral Blood Lymphocytes

To move closer to the goal of individualized risk prediction for prostate cancer, we used an in vivo canine model to evaluate whether the susceptibility of peripheral blood lymphocytes (PBLs) to oxidative stress-induced DNA damage could identify those individuals with the highest prostatic DNA damage. This hypothesis was tested in a population of 69 elderly male beagle dogs after they had completed a 7-month randomized feeding trial to achieve the broad range of dietary selenium status observed in U.S. men. The alkaline Comet assay was used to directly compare the extent of DNA damage in PBLs with prostatic DNA damage in each dog. Using stepwise logistic regression, the sensitivity of PBLs to oxidative stress challenge with hydrogen peroxide (H(2)O(2)) predicted dogs in the highest tertile of prostatic DNA damage. Dogs with PBLs highly sensitive to H(2)O(2) were 7.6 times [95% confidence interval (95% CI), 1.5-38.3] more likely to have high prostatic DNA damage than those in the H(2)O(2)-resistant group. This risk stratification was observed in multivariate analysis that considered other factors that might influence DNA damage, such as age, toenail selenium concentration, and serum testosterone concentration. Our data show that the sensitivity of PBLs to oxidative stress challenge, but not endogenous DNA damage in PBLs, provides a noninvasive surrogate marker for prostatic DNA damage. These findings lend support to the concept that oxidative stress contributes to genotoxic damage, and that oxidative stress challenge may stratify men for prostate cancer risk.

Selenium and Diabetes: More Bad News for Supplements

In this issue, Stranges and colleagues report an increased risk for diabetes among participants randomly assigned to receive selenium supplements in the Nutritional Prevention of Cancer trial. The ...