Toenail selenium levels and prevalence of dyslipidaemia among Korean adults.

Multiple studies have elucidated the antioxidant properties of Se, which are now well known among the nutrition and biomedical science communities. Recently, considerable interest has been focused on the possible association between Se exposure and risk of metabolic disease, such as lipid dysregulation; however, there is limited epidemiological data on this topic. The present study aimed to investigate associations between toenail Se levels and dyslipidaemia or individual lipid levels, and to examine the effect of dietary supplement use on these associations. We analysed baseline data from a cohort in the Yeungnam area, including 232 men and 269 women. Information on demographic, dietary and lifestyle characteristics was obtained through a self-reported questionnaire. Se levels in toenail specimens were measured using neutron activation analysis. Fasting blood lipid levels were measured during medical examinations. After adjusting for multiple confounding variables, we observed no association between toenail Se levels and dyslipidaemia or individual lipid profiles. However, the association was modified by dietary supplement use. Among the supplement users, higher toenail Se levels were associated with a higher prevalence of lipid dysregulation, whereas non-users exhibited a lower prevalence of lipid dysregulation. Associations between toenail Se levels, lipid levels and dyslipidaemia may be influenced by taking dietary supplements. Future large-scale, prospective cohort studies should be conducted to further evaluate the association between Se levels in the body and metabolic health effects in light of increasing rates of dietary supplement use.

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

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.).

Serum zinc and prostate cancer risk in a nested case-control study: The multiethnic cohort.

BACKGROUND: Experimental studies have provided evidence that zinc has a protective effect against development and progression of prostate cancer. However, epidemiological studies have reported inconsistent findings. We evaluated the association between prediagnostic serum zinc and prostate cancer risk in a cohort of multiethnic population. METHODS: This case-control study is nested within the Multiethnic Cohort of African Americans, Native Hawaiians, Japanese Americans, Latinos, and whites in Hawaii and California. The analysis included 392 prostate cancer cases and 783 controls matched on age, race/ethnicity, date/time of blood draw and fasting status. Conditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI). RESULTS: The mean serum zinc concentrations did not significantly differ between cases (94.9 µg/dl) and controls (93.9 µg/dl). No association was found between serum zinc levels and prostate cancer either overall or by tumor stage/grade. In ethnic-specific analyses, positive associations were found in Japanese Americans (OR for the highest vs. the lowest tertile = 2.59, 95% CI: 1.09-6.17) and Latinos (OR = 2.74, 95% CI: 1.05-7.10), whereas no association was observed in African Americans and whites. CONCLUSIONS: We found no evidence to support an inverse relationship between serum zinc and prostate cancer risk, and, to the contrary, found a suggestion in the ethnic-specific results of a possible increase in risk; however, blood concentrations of zinc may not adequately reflect the levels in prostate tissue. Further study with a larger sample size, and if possible, with assessment of zinc tissue levels, is warranted to confirm these findings.

Diet and toenail arsenic concentrations in a New Hampshire population with arsenic-containing water.

BACKGROUND: Limited data exist on the contribution of dietary sources of arsenic to an individual's total exposure, particularly in populations with exposure via drinking water. Here, the association between diet and toenail arsenic concentrations (a long-term biomarker of exposure) was evaluated for individuals with measured household tap water arsenic. Foods known to be high in arsenic, including rice and seafood, were of particular interest. METHODS: Associations between toenail arsenic and consumption of 120 individual diet items were quantified using general linear models that also accounted for household tap water arsenic and potentially confounding factors (e.g., age, caloric intake, sex, smoking) (n = 852). As part of the analysis, we assessed whether associations between log-transformed toenail arsenic and each diet item differed between subjects with household drinking water arsenic concentrations <1 µg/L versus ≥1 µg/L. RESULTS: As expected, toenail arsenic concentrations increased with household water arsenic concentrations. Among the foods known to be high in arsenic, no clear relationship between toenail arsenic and rice consumption was detected, but there was a positive association with consumption of dark meat fish, a category that includes tuna steaks, mackerel, salmon, sardines, bluefish, and swordfish. Positive associations between toenail arsenic and consumption of white wine, beer, and Brussels sprouts were also observed; these and most other associations were not modified by exposure via water. However, consumption of two foods cooked in water, beans/lentils and cooked oatmeal, was more strongly related to toenail arsenic among those with arsenic-containing drinking water (≥1 µg/L). CONCLUSIONS: This study suggests that diet can be an important contributor to total arsenic exposure in U.S. populations regardless of arsenic concentrations in drinking water. Thus, dietary exposure to arsenic in the US warrants consideration as a potential health risk.

SLC39A2 and FSIP1 polymorphisms as potential modifiers of arsenic-related bladder cancer.

Arsenic is a carcinogen that contaminates drinking water worldwide. Accumulating evidence suggests that both exposure and genetic factors may influence susceptibility to arsenic-induced malignancies. We sought to identify novel susceptibility loci for arsenic-related bladder cancer in a US population with low to moderate drinking water levels of arsenic. We first screened a subset of bladder cancer cases using a panel of approximately 10,000 non-synonymous single nucleotide polymorphisms (SNPs). Top ranking hits on the SNP array then were considered for further analysis in our population-based case-control study (n = 832 cases and 1,191 controls). SNPs in the fibrous sheath interacting protein 1 (FSIP1) gene (rs10152640) and the solute carrier family 39, member 2 (SLC39A2) in the ZIP gene family of metal transporters (rs2234636) were detected as potential hits in the initial scan and validated in the full case-control study. The adjusted odds ratio (OR) for the FSIP1 polymorphism was 2.57 [95% confidence interval (CI) 1.13, 5.85] for heterozygote variants (AG) and 12.20 (95% CI 2.51, 59.30) for homozygote variants (GG) compared to homozygote wild types (AA) in the high arsenic group (greater than the 90th percentile), and unrelated in the low arsenic group (equal to or below the 90th percentile) (P for interaction = 0.002). For the SLC39A2 polymorphism, the adjusted ORs were 2.96 (95% CI 1.23, 7.15) and 2.91 (95% CI 1.00, 8.52) for heterozygote (TC) and homozygote (CC) variants compared to homozygote wild types (TT), respectively, and close to one in the low arsenic group (P for interaction = 0.03). Our findings suggest novel variants that may influence risk of arsenic-associated bladder cancer and those who may be at greatest risk from this widespread exposure.

Associations between toenail arsenic concentration and dietary factors in a New Hampshire population.

BACKGROUND: Dietary factors such as folate, vitamin B12, protein, and methionine are important for the excretion of arsenic via one-carbon metabolism in undernourished populations exposed to high levels of arsenic via drinking water. However, the effects of dietary factors on toenail arsenic concentrations in well-nourished populations exposed to relatively low levels of water arsenic are unknown. METHODS: As part of a population-based case-control study of skin and bladder cancer from the USA, we evaluated relationships between consumption of dietary factors and arsenic concentrations in toenail clippings. Consumption of each dietary factor was determined from a validated food frequency questionnaire. We used general linear models to examine the associations between toenail arsenic and each dietary factor, taking into account potentially confounding effects. RESULTS: As expected, we found an inverse association between ln-transformed toenail arsenic and consumption of vitamin B12 (excluding supplements) and animal protein. Unexpectedly, there were also inverse associations with numerous dietary lipids (e.g., total fat, total animal fat, total vegetable fat, total monounsaturated fat, total polyunsaturated fat, and total saturated fat). Finally, increased toenail arsenic concentrations were associated with increased consumption of long chain n-3 fatty acids. CONCLUSION: In a relatively well-nourished population exposed to relatively low levels of arsenic via water, consumption of certain dietary lipids may decrease toenail arsenic concentration, while long chain n-3 fatty acids may increase toenail arsenic concentration, possibly due to their association with arsenolipids in fish tissue.

Toenail mercury levels positively correlate with obesity and abdominal obesity among Korean adults.

BACKGROUND: Although previous studies have shown that short-term exposure to mercury is associated with obesity, it should be noted that mercury is not easily released and that it constantly accumulates in the body. However, few studies have explored the association between chronic mercury exposure and obesity. This study aimed to examine the association between chronic mercury exposure and obesity in Korean adults. METHODS: The study used baseline data from the Trace Element Study of Korean Adults in Yeungnam area. A total of 495 participants aged 40-69 years who provided the required information (demographic, diet, lifestyle, toenail mercury levels, and health examination results) were included. Toenail mercury levels were measured using neutron-activation analysis. Body mass index and waist circumference were obtained from medical examination. Multivariable-adjusted logistic regression and restricted cubic spline regression were used in the analysis. RESULTS: In the fully adjusted logistic regression models, participants with the highest toenail mercury levels had a higher prevalence of obesity (odds ratio [OR]: 3.26, 95 % confidence interval [CI]: 1.79-5.93) and abdominal obesity (OR: 2.30, 95 % CI: 1.15-4.59). In the cubic spline regression model, linear relationships were confirmed between increased toenail mercury levels and higher prevalence of obesity and abdominal obesity (all p > 0.05 for nonlinearity). CONCLUSIONS: In summary, chronic mercury exposure was associated with higher prevalence of obesity and abdominal obesity in Korean adults. Therefore, the development of public health interventions against environmental exposure of foods is required to manage and prevent obesity.

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.

Correlation between selenium concentrations and glutathione peroxidase activity in serum and human prostate tissue.

BACKGROUND: Low serum selenium concentration has been associated with increased risk of prostate cancer. A possible mechanism is through the antioxidant activity of selenoenzymes. However, the effect of selenium intake on selenoenzymes at target tissues is not well established. Hence, we investigated the correlation between serum and prostate tissue selenium concentrations and prostate tissue activity of glutathione peroxidase (GPX), a major selenoenzyme with antioxidant properties. METHODS: In an ongoing study investigating gene expression in prostate tissue, we measured serum selenium concentration in 98 men using atomic absorption spectrometry. Of these men, we selected 12 men with the highest and 12 men with the lowest serum selenium concentrations and measured selenium concentration and GPX activity in fresh frozen prostate tissue using the cyclic neutron activation analysis and a direct spectrophotometric procedure, respectively. RESULTS: The mean serum selenium concentrations among low and high selenium groups were 123.7 +/- 5.9 and 196.7 +/- 16.6 microg/L (P < 0.0001), respectively. The corresponding mean prostate tissue selenium concentrations were 1.39 +/- 0.28 and 1.65 +/- 0.42 microg/g (P = 0.08), resulting in a positive correlation between serum and prostate tissue selenium concentrations (r = 0.56, P = 0.02). The mean prostate tissue GPX activity was non-significantly greater in the low serum selenium group (32.2 +/- 8.4 U/g protein) than in the high serum selenium group (29.6 +/- 5.9 U/g protein) (P = 0.39) and it was not correlated with serum or prostate tissue selenium concentrations (r = -0.22, P = -0.37 for serum and r = -0.33, P = 0.18 for prostate tissue). CONCLUSION: Serum and prostate tissue selenium concentrations were moderately correlated. In this population with relatively high selenium concentration, neither prostate tissue nor serum selenium concentrations were associated with prostate tissue GPX activity.

Exposure to Trace Elements and Risk of Skin Cancer: A Systematic Review of Epidemiologic Studies.

Exposure to environmental trace elements has been studied in relation to many cancers. However, an association between exposure to trace elements and skin cancer remains less understood. Therefore, we conducted a systematic review of published epidemiologic literature examining the association between exposure to trace elements, and risk of melanoma and keratinocyte carcinoma in humans. We identified epidemiologic studies investigating exposure to arsenic, cadmium, chromium, copper, iron, selenium, and zinc and risk of skin cancer in humans. Among the minerals, arsenic, selenium, and zinc had more than five studies available. Exposure to arsenic was associated with increased risk of keratinocyte carcinoma, while too few studies existed on melanoma to draw conclusions. Exposure to selenium was associated with possible increased risk of keratinocyte carcinoma. Studies of zinc and skin cancer were case-control in design and were found to have inconsistent associations. The data on the association between cadmium, chromium, copper, and iron and risk of skin cancer remain too sparse to draw any conclusions. In summary, epidemiologic studies on exposure to trace elements and cutaneous malignancies are limited. Studies with larger sample sizes and prospective designs are warranted to improve our knowledge of trace elements and skin cancer.

A Prospective Study of Toenail Trace Element Levels and Risk of Skin Cancer.

BACKGROUND: Few epidemiologic studies have investigated trace element exposure and skin cancer risk. METHODS: Toenail levels of mercury, selenium, chromium, iron, and zinc were measured from 6,708 women in the Nurses' Health Study (1984-2012) and 3,730 men in the Health Professionals Follow-up Study (1986-2012) with data from prior nested case-control studies. Participants were free of skin cancer at toenail collection and followed for incident basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and melanoma. Cox proportional hazards models were used to compute hazard ratios (HR) and 95% confidence intervals (CI) of skin cancer associated with the elements in each study. We calculated pooled multivariable HRs using a fixed-effects model. During 26 to 28 years of follow-up, 2,433 BCC, 334 SCC, and 130 melanoma cases were documented. RESULTS: Higher toenail mercury levels were associated with risk of BCC [pooled HR for top vs. bottom quintiles = 1.34 (95% CI, 1.18-1.52), P trend < 0.0001]. Similar direct associations were found with risks of SCC [pooled HR for top vs. bottom quartiles = 1.41 (95% CI, 1.03-1.94), P trend = 0.04] and melanoma [pooled HR for top vs. bottom quartiles = 1.88 (95% CI, 1.12-3.16), P trend = 0.02]. Chromium was positively associated with BCC in women only. No associations were found between other metals and skin cancer risk. CONCLUSIONS: Our prospective data found that increased toenail mercury concentrations were associated with increased skin cancer risk. IMPACT: If our novel findings are confirmed, mercury may play a role in skin carcinogenesis.

The risk of developing lung cancer associated with antioxidants in the blood: ascorbic acids, carotenoids, alpha-tocopherol, selenium, and total peroxyl radical absorbing capacity.

Lung cancer cases diagnosed during the period 1975 through 1993 and matched controls were identified in the rosters of Washington County, Maryland residents who had donated blood for a serum bank in 1974 or 1989. Plasma from participants in the 1989 project was assayed for ascorbic acid; serum or plasma was assayed for participants in either project for alpha- and beta-carotene, cryptoxanthin, lutein/zeaxanthin, lycopene, alpha-tocopherol, selenium, and peroxyl radical absorption capacity. Among the total group of 258 cases and 515 controls, serum/plasma concentrations were significantly lower among cases than controls for cryptoxanthin, beta-carotene, and lutein/zeaxanthin with case-control differences of -25.5, -17.1, and -10.1%, respectively. Modest nonsignificant case-control differences in a protective direction were noted for alpha-carotene and ascorbic acid. There were only trivial differences for lycopene, alpha-tocopherol, selenium, and peroxyl radical absorption capacity. Findings are reported for males and females and for persons who had never smoked cigarettes, former smokers, and current smokers at baseline. These results and those from previous studies suggest that beta-carotene is a marker for some protective factor(s) against lung cancer; that cryptoxanthin, alpha-carotene, and ascorbic acid need to be investigated further as potentially protective factors or associates of a protective factor; and that lycopene, alpha-tocopherol, selenium, and peroxyl radical absorption capacity are unlikely to be associated with lung cancer risk. Until specific preventive factors are identified, the best protection against lung cancer is still the avoidance of airborne carcinogens, especially tobacco smoke; second best is the consumption of a diet rich in fruits and vegetables.

Effect of dietary selenium on the promotion of hepatocarcinogenesis by 3,3', 4,4'-tetrachlorobiphenyl and 2,2', 4,4', 5,5'-hexachlorobiphenyl.

Polychlorinated biphenyls (PCBs) are persistent organic pollutants that have promoting activity in the liver. PCBs induce oxidative stress, which may influence carcinogenesis. Epidemiological studies strongly suggest an inverse relationship between dietary selenium (Se) and cancer. Despite evidence linking Se deficiency to hepatocellular carcinoma and liver necrosis, the underlying mechanisms for Se cancer protection in the liver remain to be determined. We examined the effect of dietary Se on the tumor promoting activities of two PCBs congeners, 3,3', 4,4'-tetrachlorobiphenyl (PCB-77) and 2,2', 4,4', 5,5'-hexachlorobiphenyl (PCB-153) using a 2-stage carcinogenesis model. An AIN-93 torula yeast-based purified diet containing 0.02 (deficient), 0.2 (adequate), or 2.0 mg (supplemental) selenium/kg diet was fed to Sprague-Dawley female rats starting ten days after administering a single dose of diethylnitrosamine (150 mg/kg). After being fed the selenium diets for 3 weeks, rats received four i.p. injections of either PCB-77 or PCB-153 (150 micromol/kg) administered every 14 days. The number of placental glutathione S-transferase (PGST)-positive foci per cm(3) and per liver among the PCB-77-treated rats was increased as the Se dietary level increased. Unlike PCB-77, rats receiving PCB-153 did not show the same Se dose-response effect; nevertheless, Se supplementation did not confer protection against foci development. However, the 2.0 ppm Se diet reduced the mean focal volume, indicating a possible protective effect by inhibiting progression of preneoplastic lesions into larger foci. Cell proliferation was not inhibited by Se in the liver of the PCB-treated groups. Se did not prevent the PCB-77-induced decrease of hepatic Se and associated reduction in glutathione peroxidase (GPx) activity. In contrast, thioredoxin reductase (TrxR) activity was not affected by the PCBs treatment or by Se supplementation. These findings indicate that Se does not inhibit the number of PGST-positive foci induced during promotion by PCBs, but that the size of the lesions may be inhibited. The effects of Se on altered hepatic foci do not correlate with its effects on GPx and TrxR.

Toenail Chromium Concentration and Metabolic Syndrome among Korean Adults.

Although in vivo and in vitro studies have shown that chromium has protective effects against metabolic diseases, few studies have examined this association in humans. The present study examined chronic chromium (Cr) exposure among Koreans based on the measurement of toenail Cr concentrations, and analyzed the associations between toenail Cr concentrations and metabolic syndrome (MetS) and its components. We conducted a cross-sectional analysis using baseline data from the prospective cohort study in the Yeungnam area of South Korea that included 232 men and 268 women. Toenail Cr concentration was quantified by neutron activation analysis, and metabolic biomarker levels were obtained through medical examinations. The odd ratios (OR) of prevalent MetS and its components in correlation with Cr concentrations were calculated using multivariable logistic regression. After multiple confounding variables were adjusted for, participants with higher concentrations of Cr had a prevalence rate of MetS similar to those with lower concentrations (OR, 1.84; 95% confidence interval, 0.65-5.23). Our results do not support an association between long-term exposure to Cr and a lower prevalence of MetS in Koreans, whose Cr concentrations are relatively low compared to those of populations in Europe and the United States.

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.

Mercury and the risk of coronary heart disease in men.

BACKGROUND: A high dietary intake of mercury from consumption of fish has been hypothesized to increase the risk of coronary heart disease. METHODS: Using a nested case-control design, we investigated the association between mercury levels in toenails and the risk of coronary heart disease among male health professionals with no previous history of cardiovascular disease or cancer who were 40 to 75 years of age in 1986. Toenail clippings were collected in 1987 from 33,737 cohort members, and during five years of follow-up, we documented 470 cases of coronary heart disease (coronary-artery surgery, nonfatal myocardial infarction, and fatal coronary heart disease). Each patient was matched according to age and smoking status with a randomly selected control subject. RESULTS: The mercury level was significantly correlated with fish consumption (Spearman r=0.42, P<0.001), and the mean mercury level was higher in dentists than in nondentists (mean, 0.91 and 0.45 microg per gram, respectively; P<0.001). After age, smoking, and other risk factors for coronary heart disease had been controlled for, the mercury level was not significantly associated with the risk of coronary heart disease. When the highest and lowest quintiles of mercury level were compared, the relative risk of coronary heart disease was 0.97 in the highest level (95 percent confidence interval, 0.63 to 1.50; P value for trend=0.78). Adjustment for intake of n-3 fatty acids from fish did not appreciably change these results. CONCLUSIONS: Our findings do not support an association between total mercury exposure and the risk of coronary heart disease, but a weak relation cannot be ruled out.

Toenail and plasma levels as biomarkers of selenium exposure.

PURPOSE: Both blood and toenail selenium are used to assess selenium exposure in epidemiologic studies. Little is known about the relationship of these biomarkers with each other or about whether there are differences in the relationships of these biomarkers with diet, supplement use, or participant characteristics. METHODS: Data are from 220 participants in a large cohort study of supplement use and cancer risk. Measures of selenium exposure included supplement use (current and 10-year) from a self-administered questionnaire, an inventory of currently used supplements (multivitamins and single supplements), dietary intake from a food frequency questionnaire (FFQ), and selenium concentration in toenails and plasma. RESULTS: Plasma and toenail selenium concentrations were significantly correlated (r=.56 [95% confidence interval: .46, .64]). Supplemental selenium was the strongest predictor of both selenium biomarkers, and these associations were slightly stronger when based on the supplement inventory and 10-year self-reported use compared to current self-reported use. Correlations of current and 10-year questionnaire dose and inventory dose with toenail selenium were .26, .36, and .33; for plasma selenium, these were .27, .36, and .36. Neither dietary selenium nor any participant characteristics, except smoking, was related to either biomarker. Current smokers had lower toenail, but not plasma, selenium levels compared to nonsmokers (.89 versus 1.03 microg/g, p = .03); however, the difference was not significant after control for supplement use (p = .09). CONCLUSIONS: Both toenail and plasma selenium levels similarly reflect selenium intake exposure. There do not appear to be independent associations of toenail or plasma selenium with FFQ-derived selenium intakes, health-related behaviors, or demographic characteristics.

Effects of dietary selenium supplementation on DNA damage and apoptosis in canine prostate.

The trace mineral selenium inhibits cancer development in a variety of experimental animal models. We used an in vivo canine model to evaluate the effects of dietary selenium supplementation on DNA damage in prostate tissue and on apoptosis in prostate epithelial cells. Sexually intact elderly male beagle dogs were randomly assigned to receive an unsupplemented diet (control group) or diets that were supplemented with selenium (treatment group), either as selenomethionine or as high-selenium yeast at 3 micro g/kg or 6 micro g/kg body weight per day for 7 months. The extent of DNA damage in prostate cells and in peripheral blood lymphocytes, as determined by the alkaline comet assay, was lower among the selenium-supplemented dogs than among the control dogs (prostate P<.001; peripheral blood lymphocytes P =.003; analysis of variance) but was not associated with the activity of the antioxidant enzyme glutathione peroxidase in plasma. The median number of terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling-positive (i.e., apoptotic) prostate epithelial cells was 3.7 (interquartile range = 1.1-7.6) for the selenium-supplemented dogs and 1.7 (interquartile range = 0.2-2.8) for the control dogs ( P =.04, Mann-Whitney U test). These data suggest that dietary selenium supplementation decreases DNA damage and increases epithelial cell apoptosis within the aging canine prostate.

Lower toenail chromium in men with diabetes and cardiovascular disease compared with healthy men.

OBJECTIVE: Chromium may improve insulin sensitivity, which can modify the risk of diabetes and cardiovascular disease (CVD). Therefore, we evaluated the association between toenail chromium and CVD in diabetic men. RESEARCH DESIGN AND METHODS: We performed cross-sectional and nested case-control analyses among men aged 40-75 years within the Health Professionals Follow-up Study. The cross-sectional analysis compared men with diabetes only (n = 688), diabetes with prevalent CVD (n = 198), and healthy control subjects (n = 361). The nested case-control study included 202 men with baseline diabetes who developed incident CVD and 361 matched control subjects. RESULTS: Mean toenail chromium (microg/g) was 0.71 in healthy control subjects, 0.61 in diabetes-only subjects, and 0.52 in diabetic subjects with prevalent CVD (P for trend = 0.003). In the cross-sectional analysis, the multivariate odds ratio (OR) between extreme quartiles was 0.74 (95% CI 0.49-1.11; P for trend = 0.18), comparing diabetes only with healthy control subjects. A similar comparison between diabetic subjects with prevalent CVD and healthy control subjects yielded an OR of 0.45 (0.24-0.84; P for trend = 0.003). In the nested case-control study, comparing diabetic men with incident CVD with healthy control subjects, the multivariate OR was 0.65 (0.36-1.17; P for trend = 0.16) between extreme quartiles. When we combined prevalent and incident CVD cases among diabetic men and compared them with healthy control subjects, the OR was 0.62 (0.39-1.01; P for trend = 0.02) between extreme quartiles. CONCLUSIONS: Our results suggest that diabetic men with CVD have lower toenail chromium than healthy control subjects. However, this study could not distinguish between the effects of chromium on diabetes and those on CVD. Long-term clinical trials are needed to determine whether chromium supplementation is beneficial for preventing CVD among diabetic patients.

Prediagnostic serum selenium concentration and the risk of recurrent colorectal adenoma: a nested case-control study.

Several studies have suggested that selenium may help to prevent colorectal neoplasia. To investigate the relation between prediagnostic serum selenium concentrations and colorectal adenomas, we conducted a nested case-control study using data from a large, multicenter, adenoma prevention trial. Cases comprised a total of 276 patients who developed a colorectal adenoma between the year 1 and year 4 follow-up exam. Controls were 276 patients who did not develop an adenoma during this time interval, matched to case subjects on age, sex, and clinical center. Total and bound selenium concentrations were measured from baseline or year 1 serum samples using instrumental neutron activation analysis. We estimated the odds ratios of colorectal adenoma in relation to serum selenium concentrations adjusting for age, clinical center, and sex. Compared with the lowest quintile, the odds ratio for the highest quintile was 0.76 (95% confidence interval, 0.44-1.30) for total selenium and 0.60 (95% confidence interval, 0.34-1.05) for bound selenium, and there was no apparent trend in risk (P for trend = 0.50 for total selenium and P for trend = 0.20 for bound selenium). Thus, our findings do not indicate a clear association between serum selenium concentrations and adenoma recurrence.