The association between baseline vitamin E, selenium, and prostate cancer in the alpha-tocopherol, beta-carotene cancer prevention study. Effects of selenium supplementation for cancer prevention in patients with carcinoma of the skin. A randomized controlled trial. Nutritional Prevention of Cancer Study Group. Serum selenium and the risk of cancer, by specific sites: case-control analysis of prospective data. Plasma selenium concentration and prostate cancer risk: results from the European Prospective Investigation into Cancer and Nutrition (EPIC). Prospective study of toenail selenium levels and cancer among women. Association between alpha-tocopherol, gamma-tocopherol, selenium, and subsequent prostate cancer. Effect of selenium and vitamin E on risk of prostate cancer and other cancers: the Selenium and Vitamin E Cancer Prevention Trial (SELECT). The nutritional prevention of cancer: 400 mcg per day selenium treatment. Is serum selenium a risk factor for cancer? Plasma selenium level before diagnosis and the risk of prostate cancer development. Selenium in human mammary carcinogenesis: a case-cohort study. Relationships of serum carotenoids, retinol, alpha-tocopherol, and selenium with breast cancer risk: results from a prospective study in Columbia, Missouri (United States) Serum selenium and cancer mortality: a nested case-control study within an age- and sex-stratified sample of the Belgian adult population. A prospective cohort study on toenail selenium levels and risk of gastrointestinal cancer. Prediagnostic serum selenium in a case-control study of thyroid cancer. Serum selenium and risk of cancer. A prospective follow-up of nine years. Prospective study of serum selenium concentrations and esophageal and gastric cardia cancer, heart disease, stroke, and total death. Antioxidants and basal cell carcinoma of the skin: a nested case-control study. Study of prediagnostic selenium level in toenails and the risk of advanced prostate cancer. Association between serum selenium and the risk of cancer. A prospective study of plasma selenium levels and prostate cancer risk. Selenoprotein P in plasma in relation to cancer morbidity in middle-aged Swedish men. Is low selenium status a risk factor for lung cancer? Prediagnostic serum selenium and zinc levels and subsequent risk of lung and stomach cancer in Japan. Serum beta-carotene, vitamins A and E, selenium, and the risk of lung cancer. Serum selenium and subsequent risk of cancer among Finnish men and women. Association of plasma micronutrient levels and urinary isoprostane with risk of lung cancer: the multiethnic cohort study. Selenium and mortality in the elderly: results from the EVA study. Serum selenium and risk of prostate cancer-a nested case-control study. Toenail selenium concentrations and bladder cancer risk in women and men. No Association between toenail selenium levels and bladder cancer risk. The risk of developing lung cancer associated with antioxidants in the blood: ascorbic acid, carotenoids, alpha-tocopherol, selenium, and total peroxyl radical absorbing capacity. Dietary supplement use and risk of neoplastic progression in esophageal adenocarcinoma: a prospective study. Antioxidant supplementation and risk of incident melanomas: results of a large prospective cohort study. Prediagnostic serum selenium and risk of cancer. Serum selenium levels and all-cause, cancer, and cardiovascular mortality among US adults. Predictors of serum selenium in cigarette smokers and the lack of association with lung and prostate cancer risk. [The prevention of primary liver cancer by selenium in high risk populations]. Essential micronutrients in relation to carcinogenesis. 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. Serum tocopherols, selenium and lung cancer risk among tin miners in China. Protective role of selenium against hepatitis B virus and primary liver cancer in Qidong. Low plasma selenium as a risk factor for cancer death in middle-aged men. A preliminary report on the intervention trials of primary liver cancer in high-risk populations with nutritional supplementation of selenium in China. Serum selenium concentration associated with risk of cancer. Serum levels of selenium and retinol and the subsequent risk of cancer. Toenail selenium and risk of hepatocellular carcinoma mortality in Haimen City, China. The role of antioxidants and vitamin A in ovarian cancer: results from the Women's Health Initiative. Plasma selenium levels and risk of hepatocellular carcinoma among men with chronic hepatitis virus infection. Is serum selenium a risk factor for cancer in men only?
The association between prostate cancer and baseline vitamin E and selenium was evaluated in the trial-based cohort of the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study (n = 29,133). During up to 9 years of follow-up, 317 men developed incident prostate cancer. Multivariate Cox proportional hazards models that adjusted for intervention group, benign prostatic hyperplasia, age, smoking, and urban residence were used to evaluate associations between prostate cancer and exposures of interest. There were no significant associations between baseline serum alpha-tocopherol, dietary vitamin E, or selenium and prostate cancer overall. The associations between prostate cancer and vitamin E and some of the baseline dietary tocopherols differed significantly by alpha-tocopherol intervention status, with the suggestion of a protective effect for total vitamin E among those who received the alpha-tocopherol intervention (relative risk was 1.00, 0.68, 0.80, and 0.52 for increasing quartiles; P = 0.07). To determine whether a nutritional supplement of selenium will decrease the incidence of cancer.
                A multicenter, double-blind, randomized, placebo-controlled cancer prevention trial.
                Seven dermatology clinics in the eastern United States.
                A total of 1312 patients (mean age, 63 years; range, 18-80 years) with a history of basal cell or squamous cell carcinomas of the skin were randomized from 1983 through 1991. Patients were treated for a mean (SD) of 4.5 (2.8) years and had a total follow-up of 6.4 (2.0) years.
                Oral administration of 200 microg of selenium per day or placebo.
                The primary end points for the trial were the incidences of basal and squamous cell carcinomas of the skin. The secondary end points, established in 1990, were all-cause mortality and total cancer mortality, total cancer incidence, and the incidences of lung, prostate, and colorectal cancers.
                After a total follow-up of 8271 person-years, selenium treatment did not significantly affect the incidence of basal cell or squamous cell skin cancer. There were 377 new cases of basal cell skin cancer among patients in the selenium group and 350 cases among the control group (relative risk [RR], 1.10; 95% confidence interval [CI], 0.95-1.28), and 218 new squamous cell skin cancers in the selenium group and 190 cases among the controls (RR, 1.14; 95% CI, 0.93-1.39). Analysis of secondary end points revealed that, compared with controls, patients treated with selenium had a nonsignificant reduction in all-cause mortality (108 deaths in the selenium group and 129 deaths in the control group [RR; 0.83; 95% CI, 0.63-1.08]) and significant reductions in total cancer mortality (29 deaths in the selenium treatment group and 57 deaths in controls [RR, 0.50; 95% CI, 0.31-0.80]), total cancer incidence (77 cancers in the selenium group and 119 in controls [RR, 0.63; 95% CI, 0.47-0.85]), and incidences of lung, colorectal, and prostate cancers. Primarily because of the apparent reductions in total cancer mortality and total cancer incidence in the selenium group, the blinded phase of the trial was stopped early. No cases of selenium toxicity occurred.
                Selenium treatment did not protect against development of basal or squamous cell carcinomas of the skin. However, results from secondary end-point analyses support the hypothesis that supplemental selenium may reduce the incidence of, and mortality from, carcinomas of several sites. These effects of selenium require confirmation in an independent trial of appropriate design before new public health recommendations regarding selenium supplementation can be made From 1971 to 1975, serum specimens were obtained from 6,860 men of Japanese ancestry in Hawaii. Since then, the following numbers of newly diagnosed cases with epithelial cancer have been identified: 82 colon, 71 lung, 66 stomach, 32 rectum, and 29 urinary bladder. The stored sera of the 280 cases and of 293 randomly selected controls were tested to determine their levels of selenium. There was no association of serum selenium with lung, stomach, or rectal cancer. An increase in relative risk (RR) was noted only for subjects in the lowest quintile of selenium values, as compared to the RR for subjects in the highest quintile, for colon (RR = 1.8) and urinary bladder cancer (RR = 3.1), but neither of these RR estimates was statistically significant (P = .09 and P = .07, respectively). Further work is needed to determine whether the antioxidant properties of selenium protect against specific types of cancer. Some evidence indicates that a low selenium intake may be associated with an increased risk of prostate cancer.
                The aim of this study was to investigate the association of plasma selenium concentration with subsequent prostate cancer risk and to examine this association by stage and grade of disease and other factors.
                A nested case-control study was performed among men in the European Prospective Investigation into Cancer and Nutrition (EPIC). The association between plasma selenium concentration and prostate cancer risk was assessed in 959 men with incident prostate cancer and 1059 matched controls.
                Overall, plasma selenium concentration was not associated with prostate cancer risk; the multivariate relative risk for men in the highest fifth of selenium concentration compared with the lowest fifth was 0.96 (95% CI: 0.70, 1.31; P for trend = 0.25). There were no significant differences in the association of plasma selenium with risk when analyzed by stage or grade of disease. Similarly, the association of selenium with risk did not differ by smoking status or by plasma alpha- or gamma-tocopherol concentration.
                Plasma selenium concentration was not associated with prostate cancer risk in this large cohort of European men. Inverse associations between selenium status and cancer risk have been observed in animal studies, ecologic studies, and some case-control and prospective studies. Whereas results of some prospective studies have suggested an overall inverse relationship between selenium levels and cancer, other prospective studies have failed to confirm this finding. Prospective data on women are particularly limited because fewer women than men have been studied prospectively.
                The aim of this study was to prospectively examine the relationship between selenium levels in toenails (previously shown to reflect selenium intake) and incidence of cancer among women.
                The Nurses' Health Study cohort began in 1976 with 121,700 female nurses aged 30-55 years living in 11 U.S. states. In 1982, we requested toenail clippings from the members of the cohort, and 62,641 participants with no history of cancer returned these clippings. During 41 months of follow-up, 503 cases of cancer other than breast cancer (results previously reported) or nonmelanoma skin cancer were analyzed. For each case patient, a control subject was chosen from women who remained free of diagnosed cancer, matched by age and by date of nail return.
                No inverse association was observed between selenium levels in toenails and cancer risk. The age- and smoking-adjusted relative risk (RR), comparing the highest with the lowest quintile of toenail selenium level, was 1.44 (95% confidence interval [CI] = 0.97-2.13), and the trend across quintiles was marginally significant (two-sided P = .06). Comparing the highest with the lowest decile, the RR (age- and smoking-adjusted) was 1.77 (95% CI = 1.04-3.02). When these data were combined with the data from 434 breast cancer case patients and their matched control subjects identified in parallel from this same cohort, the RR comparing the highest with the lowest quintile was 1.24 (95% CI = 0.93-1.65). Toenail selenium level was not inversely associated with cancer at any major site, including uterine cancer, colorectal cancer, melanoma, ovarian cancer, or lung cancer (after adjusting for smoking); in fact, nonsignificant positive associations were observed at several sites.
                Toenail selenium levels were not inversely associated with cancer risk in this study.
                These data, in conjunction with previous findings of no association between toenail selenium status and breast cancer risk, strongly suggest that higher selenium intake within the range consumed by most U.S. women (as reflected by toenail selenium levels) is not protective against overall cancer incidence in women. Selenium and alpha-tocopherol, the major form of vitamin E in supplements, appear to have a protective effect against prostate cancer. However, little attention has been paid to the possible role of gamma-tocopherol, a major component of vitamin E in the U.S. diet and the second most common tocopherol in human serum. A nested case-control study was conducted to examine the associations of alpha-tocopherol, gamma-tocopherol, and selenium with incident prostate cancer.
                In 1989, a total of 10,456 male residents of Washington County, MD, donated blood for a specimen bank. A total of 117 of 145 men who developed prostate cancer and 233 matched control subjects had toenail and plasma samples available for assays of selenium, alpha-tocopherol, and gamma-tocopherol. The association between the micronutrient concentrations and the development of prostate cancer was assessed by conditional logistic regression analysis. All statistical tests were two-sided.
                The risk of prostate cancer declined, but not linearly, with increasing concentrations of alpha-tocopherol (odds ratio (highest versus lowest fifth) = 0.65; 95% confidence interval = 0.32--1.32; P(trend) =.28). For gamma-tocopherol, men in the highest fifth of the distribution had a fivefold reduction in the risk of developing prostate cancer than men in the lowest fifth (P:(trend) =.002). The association between selenium and prostate cancer risk was in the protective direction with individuals in the top four fifths of the distribution having a reduced risk of prostate cancer compared with individuals in the bottom fifth (P(trend) =.27). Statistically significant protective associations for high levels of selenium and alpha-tocopherol were observed only when gamma-tocopherol concentrations were high.
                The use of combined alpha- and gamma- tocopherol supplements should be considered in upcoming prostate cancer prevention trials, given the observed interaction between alpha-tocopherol, gamma-tocopherol, and selenium. Secondary analyses of 2 randomized controlled trials and supportive epidemiologic and preclinical data indicated the potential of selenium and vitamin E for preventing prostate cancer.
                To determine whether selenium, vitamin E, or both could prevent prostate cancer and other diseases with little or no toxicity in relatively healthy men.
                A randomized, placebo-controlled trial (Selenium and Vitamin E Cancer Prevention Trial [SELECT]) of 35,533 men from 427 participating sites in the United States, Canada, and Puerto Rico randomly assigned to 4 groups (selenium, vitamin E, selenium + vitamin E, and placebo) in a double-blind fashion between August 22, 2001, and June 24, 2004. Baseline eligibility included age 50 years or older (African American men) or 55 years or older (all other men), a serum prostate-specific antigen level of 4 ng/mL or less, and a digital rectal examination not suspicious for prostate cancer.
                Oral selenium (200 microg/d from L-selenomethionine) and matched vitamin E placebo, vitamin E (400 IU/d of all rac-alpha-tocopheryl acetate) and matched selenium placebo, selenium + vitamin E, or placebo + placebo for a planned follow-up of minimum of 7 years and a maximum of 12 years.
                Prostate cancer and prespecified secondary outcomes, including lung, colorectal, and overall primary cancer.
                As of October 23, 2008, median overall follow-up was 5.46 years (range, 4.17-7.33 years). Hazard ratios (99% confidence intervals [CIs]) for prostate cancer were 1.13 (99% CI, 0.95-1.35; n = 473) for vitamin E, 1.04 (99% CI, 0.87-1.24; n = 432) for selenium, and 1.05 (99% CI, 0.88-1.25; n = 437) for selenium + vitamin E vs 1.00 (n = 416) for placebo. There were no significant differences (all P>.15) in any other prespecified cancer end points. There were statistically nonsignificant increased risks of prostate cancer in the vitamin E group (P = .06) and type 2 diabetes mellitus in the selenium group (relative risk, 1.07; 99% CI, 0.94-1.22; P = .16) but not in the selenium + vitamin E group.
                Selenium or vitamin E, alone or in combination at the doses and formulations used, did not prevent prostate cancer in this population of relatively healthy men.
                clinicaltrials.gov identifier: NCT00006392. Nonexperimental studies suggest that individuals with higher selenium (Se) status are at decreased risk of cancer. The Nutritional Prevention of Cancer (NPC) study randomized 1,312 high-risk dermatology patients to 200-mcg/day of Se in selenized yeast or a matched placebo; selenium supplementation decreased the risk of lung, colon, prostate, and total cancers but increased the risk of nonmelanoma skin cancer. In this article, we report on a small substudy in Macon, GA, which began in 1989 and randomized 424 patients to 400-mcg/day of Se or to matched placebo. The subjects from both arms had similar baseline Se levels to those treated by 200 mcg, and those treated with 400-mcg attained plasma Se levels much higher than subjects treated with 200 mcg. The 200-mcg/day Se treatment decreased total cancer incidence by a statistically significant 25%; however, 400-mcg/day of Se had no effect on total cancer incidence. A narrow band of counties extending along the southeastern Atlantic coast from Jacksonville, Florida to Charleston, South Carolina were found to have excessively high incidence rates for esophageal cancer in non-white males. White males in the same areas have a 30% higher incidence rate for lung cancer but only average incidence rates were found for non-white males. Selenium is considered to decrease cancer risk in the animal model. In this coastal region, a study of 130 cancer patients who developed a malignancy 2-12 years after baseline examination showed no dose response relationship between baseline serum selenium levels and risk of subsequent cancer. Epidemiological studies and a randomized intervention trial suggest that the risk of prostate cancer may be reduced by selenium intake. We investigated whether plasma selenium level before diagnosis correlated with the risk of later developing prostate cancer.
                A case control study was performed on men from the Baltimore Longitudinal Study of Aging registry, including 52 with known prostate cancer and 96 age matched controls with no detectable prostatic disease. Plasma selenium was measured at an average time plus or minus standard deviation of 3.83 +/- 1.85 years before the diagnosis of prostate cancer by graphite furnace atomic absorption spectrophotometry. Adjusted odds ratio and 95% confidence interval were computed with logistic regression.
                After correcting for years before diagnosis, body mass index, and smoking and alcohol use history, higher selenium was associated with a lower risk of prostate cancer. Compared with the lowest quartile of selenium (range 8.2 to 10.7 microg./dl.), the odds ratios of the second (10.8 to 11.8), third (11.9 to 13.2) and fourth (13.3 to 18.2) quartiles were 0.15 (95% confidence interval 0.05 to 0.50), 0.21 (0.07 to 0.68) and 0.24 (0.08 to 0.77, respectively, p =0.01). Furthermore, plasma selenium decreased significantly with patient age (p <0.001).
                Low plasma selenium is associated with a 4 to 5-fold increased risk of prostate cancer. These results support the hypothesis that supplemental selenium may reduce the risk of prostate cancer. Because plasma selenium decreases with patient age, supplementation may be particularly beneficial to older men. In a prospective study conducted on the island of Guernsey a cohort of 5162 ostensibly healthy women was enrolled between 1967 and 1976. Blood samples were drawn from each participant, who also completed a questionnaire, which provided information on established risk indicators in human mammary carcinogenesis. Plasma selenium levels were measured in 46 breast cancer cases diagnosed a mean of 11 (S.D. 4) years after entry into the study cohort and in an age-stratified sample of 138 women drawn from the study base. Plasma selenium level in the cases was 109 (28) micrograms/l and in the base sample 103 (22) micrograms/l (95% confidence interval for the overall difference, -2 to 14 micrograms/l). The adjusted relative risk of developing breast cancer in the different quartiles of the selenium distribution was 0.80, 0.79, 0.72 and 1.00, respectively. Thus, in the present study selenium was not a strong indicator of human breast cancer risk. To evaluate relationships of serum carotenoids, alpha-tocopherol, selenium, and retinol with breast cancer prospectively, we conducted a case-control study nested in a cohort from the Breast Cancer Serum Bank in Columbia, Missouri (United States). Women free of cancer donated blood to this bank in 1977-87. During up to 9.5 years of follow-up (median = 2.7 years), 105 cases of histologically confirmed breast cancer were diagnosed. For each case, two women alive and free of cancer at the age of the case's diagnosis and matched on age and date of blood collection were selected as controls. A nonsignificant gradient of decreasing risk of breast cancer with increasing serum beta-cryptoxanthin was apparent for all women. Serum lycopene also was associated inversely with risk, and among women who donated blood at least two years before diagnosis, a significant gradient of decreasing breast cancer risk with increasing lycopene concentration was evident. A marginally significant gradient of decreasing risk with increasing serum lutein/zeaxanthin also was apparent among these women. We did not observe any evidence for protective effects of alpha- and beta-carotene, alpha-tocopherol, retinol, or selenium for breast cancer. Results of this study suggest that the carotenoids beta-cryptoxanthin, lycopene, and lutein/zeaxanthin may protect against breast cancer. To study the predictive power of serum selenium with regard to cancer mortality in a large sample of the Belgian population given the lack of coherence in the results of observational epidemiological studies in this domain.
                A prospective case-control study within a stratified sample of the Belgian male and female population.
                A total of 201 cases randomly selected from all cancer deaths (N=343) during a 10-y mortality follow-up of a large age- and sex-stratified sample of the total Belgian population aged 25-74 y were matched for age and gender with 603 controls.
                Conditional logistic regression for both univariate and multivariate analyses using tertile distribution of serum selenium in controls. Odds ratios (ORs) are adjusted for 10 baseline characteristics.
                Unadjusted ORs of cancer deaths taking the highest tertile of serum selenium as a reference: in male subjects T1/T3 is 2.2 (CI 1.3-3.7) (P for trend 0.011), whereas in female subjects a nonsignificant OR of 0.8 is observed. In multivariate analyses, no significant modifications of the ORs are observed for the predictive relation of serum selenium with cancer mortality. Besides serum selenium, beta-carotene intake and smoking are independent predictors in male subjects.
                In this nested case-control study of a stratified sample from the Belgian population, serum selenium is an independent predictor of cancer mortality in male subjects only, in a country with rather high serum selenium levels with respect to most other European countries. Various animal studies and ecologic studies suggest an inverse association between low dietary selenium intake and risk of various types of cancer.
                The goal of this prospective cohort study was to investigate the association between toenail selenium levels and risks of stomach cancer and colorectal cancer.
                Our cohort study on diet and cancer started in The Netherlands in 1986 with enrollment of 120,852 subjects aged 55-69 years. Of this number, 58,279 were men and 62,573 were women. Following the case-cohort approach for analysis of the data, we randomly selected from the cohort a subcohort of 3500 subjects (1688 men and 1812 women). After 3.3 years of follow-up, 155 incident cases of microscopically confirmed stomach cancer, 313 cases of colon cancer, and 166 cases of rectal cancer had been detected in the cohort. Toenail selenium data were available for 104 patients with stomach cancer, 234 with colon cancer, and 113 with rectal cancer and for 2459 subjects from the subcohort.
                In a multivariate analysis, the relative rates (RRs) of stomach cancer for subjects in increasing quintiles of toenail selenium level were 1.00, 0.44, 0.59, 0.84, and 0.64 (trend, P = .491). For men, there was some evidence for an inverse association between toenail selenium levels and stomach cancer: The RR for those in the highest compared with the lowest quintile of toenail selenium was 0.40 (95% confidence interval = 0.17-0.96), but the trend was not statistically significant (P = .136). For stomach cancer in women, there was no negative association with toenail selenium levels. Toenail selenium level was not associated with the risk of colon or rectal cancer. After exclusion of cases diagnosed in the 1st year of follow-up, the RRs of colon cancer for increasing quintiles of toenail selenium were 1.00, 1.27, 1.17, 0.75, and 1.07 (trend, P = .544); for rectal cancer, RR estimates were 1.00, 1.73, 0.83, 1.58, and 1.12 (trend, P = .890).
                These data support a suggestive but inconsistent inverse association between selenium levels and risk of stomach cancer. Our findings, like those of other studies, do not suggest an inverse association with risk of colorectal cancer. Sera from 43 persons who developed thyroid cancer on an average 4.8 years after blood sampling were compared with sera from controls. Three controls per case matched for sex, age, place of residence and year of blood sampling, with regard to serum selenium and serum copper. Cases were significantly lower in serum selenium than controls, and the estimated odds ratio of thyroid cancer increased from 1 for levels greater than or equal to 1.65 mumol/l, to 6.1 for levels 1.26-1.64 mumol/l, to 7.7 for levels less than or equal to 1.25 mumol/l. When time from blood sampling to diagnosis of the case was considered, it could be shown that the protective effect of high serum selenium concentrations was restricted to the last (less than 7) years prior to the diagnosis of thyroid cancer. The serum selenium concentration of cases tended to decrease relative to controls the shorter time was from blood sampling to the diagnosis. There was no difference between cases and controls with regard to serum copper. The association between serum selenium concentration and the risk of cancer was studied in 1110 men aged 55 to 74 years in two rural areas of Finland. The men were followed-up prospectively for 9 years and there were 109 new cases of cancer, with the cases of the first follow-up year excluded. The serum selenium concentrations were adjusted for age, area, smoking, serum cholesterol, and alcohol intake. The patients had a slightly lower adjusted mean serum selenium than the subjects without cancer at the end of the follow-up (+/- standard error of mean) 53.9 +/- 1.5 and 55.3 +/- 0.5 micrograms/l, respectively. The relative risks of cancer were essentially the same when these were calculated in the tertiles of the serum selenium distribution. Thirty-seven men had a history of cancer at baseline or had cancer diagnosed during the first follow-up year and their adjusted mean serum selenium was 49.4 +/- 2.6 micrograms/l, which was significantly lower (P less than 0.05) than that of the subjects without cancer during the follow-up. We previously reported an inverse association between prediagnostic serum selenium concentrations and the risk of esophageal squamous cell carcinoma (ESCC) and gastric cardia cancer (GCC) but not gastric noncardia cancer (GNCC) in a nested study from the Nutrition Intervention Trial in Linxian, China.
                We examined the relation between baseline serum selenium and the subsequent risk of death from ESCC, GCC, GNCC, heart disease (HD), stroke, and total death over 15 y of follow-up (1986-2001).
                We measured baseline serum selenium concentrations in 1103 subjects randomly selected from a larger trial cohort. We identified 516 deaths during the 15-y follow up, including 75 from ESCC, 36 from GCC, 116 from HD, and 167 from stroke. Relative risks (RRs) and 95% CIs were estimated by using Cox proportional hazards regression models. Reported RRs estimated the change in risk conferred by a 25% increase in serum selenium relative to the population distribution. All estimates were adjusted for sex, age, smoking, drinking, and serum cholesterol.
                We found significant inverse associations between baseline serum selenium and death from ESCC (RR: 0.83; 95% CI: 0.71, 0.98) and GCC (0.75; 0.59, 0.95). Trends toward inverse associations were noted for death from HD (0.89; 0.78, 1.01; P = 0.07), but no association was noted for total death (0.96; 0.90, 1.02) or stroke (0.99; 0.88, 1.11).
                Population-wide selenium supplementation in the region of China with low serum selenium and high incidences of ESCC and GCC merits serious consideration. To investigate the relationship between basal cell carcinoma (BCC) and antioxidant nutrients, specifically carotenoids, vitamin E and selenium.
                The Nambour Skin Cancer Study is an ongoing, community-based study of randomly selected adult residents of a township in sub-tropical Queensland, Australia. Using a nested case-control design, incident cases of BCC (n=90) were compared with age and sex matched controls (n=90). Dietary exposure was measured using food frequency questionnaire estimates of intake as well as serum biomarkers. Other determinants of skin cancer including sun exposure were also considered. Dietary intakes were adjusted for energy intake, and serum carotenoids and vitamin E were adjusted for serum cholesterol. Odds ratios were calculated across quartiles of dietary intake and serum biomarkers and linear trends were assessed using logistic regression, adjusting for age, sex and supplement use.
                In this prospective study no significant associations were found between BCC and carotenoids, vitamin E or selenium, as measured by serum biomarkers or dietary intake, although there was a suggestion of a positive association with lutein intake. In a recent randomized intervention trial, the risk of prostate cancer for men receiving a daily supplement of 200 microg selenium was one third of that for men receiving placebo. By use of a nested case-control design within a prospective study, i.e., the Health Professionals Follow-Up Study, we investigated the association between risk of prostate cancer and prediagnostic level of selenium in toenails, a measure of long-term selenium intake.
                In 1986, 51,529 male health professionals aged 40-75 years responded to a mailed questionnaire to form the prospective study. In 1987, 33,737 cohort members provided toenail clippings. In 1988, 1990, 1992, and 1994, follow-up questionnaires were mailed. From 1989 through 1994, 181 new cases of advanced prostate cancer were reported. Case and control subjects were matched by age, smoking status, and month of toenail return. Selenium levels were determined by neutron activation. All P values are two-sided.
                The selenium level in toenails varied substantially among men, with quintile medians ranging from 0.66 to 1.14 microg/g for control subjects. When matched case-control data were analyzed, higher selenium levels were associated with a reduced risk of advanced prostate cancer (odds ratio [OR] for comparison of highest to lowest quintile = 0.49; 95% confidence interval [CI] = 0.25-0.96; P for trend = .11). After additionally controlling for family history of prostate cancer, body mass index, calcium intake, lycopene intake, saturated fat intake, vasectomy, and geographical region, the OR was 0.35 (95% CI = 0.16-0.78; P for trend = .03).
                Our results support earlier findings that higher selenium intakes may reduce the risk of prostate cancer. Further prospective studies and randomized trials of this relationship should be conducted. A matched-pair analysis was conducted with data based on a prospective six-year follow-up of a random population sample to study the association between serum selenium and the risk of cancer. Case-control pairs were from a population, after exclusions, of 8,113 persons examined in 1972 from two counties in eastern Finland. Cases were 31- to 59-year-old men and women initially free of cancer. One control was matched to each case according to age, gender, daily tobacco consumption, and serum cholesterol concentration. The mean serum selenium of the 128 cases was 50.5 micrograms/liter and that of the controls was 54.3 micrograms/liter (p = 0.012 for difference). When the residual variation in tobacco consumption and serum cholesterol as well as that in four other possible confounders was allowed for in a multiple logistic model, serum selenium of less than 45 micrograms/liter was associated with a relative risk of cancer of 3.1 (95% confidence interval, 1.5-6.7, p less than 0.01). These data support the hypothesis that selenium deficiency increases the risk of certain cancers in middle-aged persons. Epidemiologic studies suggest that low selenium levels are associated with an increased incidence of prostate cancer, although results are conflicting. We examined the association between pre-diagnostic plasma selenium levels and risk of prostate cancer in men enrolled in the Physicians' Health Study.
                Using plasma samples obtained in 1982 from healthy men enrolled in the study, we conducted a nested case-control study among 586 men diagnosed with prostate cancer during 13 years of follow-up and 577 control subjects. Odds ratios (ORs) and 95% confidence intervals (CIs) for the risk of prostate cancer in pre- (before October 1990) and post- (after October 1990) prostate-specific antigen (PSA) screening eras were calculated using multivariable logistic regression.
                Pre-diagnostic plasma selenium levels were inversely associated with risk of advanced prostate cancer (5th versus 1st quintile OR = 0.52, 95% CI = 0.28 to 0.98; P(trend) =.05), even among men diagnosed after 1990 (5th versus 1st quintile OR = 0.39, 95% CI = 0.16 to 0.97). The inverse association with prostate cancer risk was observed only for case subjects with elevated baseline PSA levels (PSA >4 ng/mL, 5th versus 1st quintile OR = 0.49, 95% CI = 0.28 to 0.86; P(trend) =.002). These inverse associations were observed in both pre- and post-PSA eras.
                The inverse association between baseline plasma selenium levels and risk of advanced prostate cancer, even among men diagnosed during the post-PSA era, suggests that higher levels of selenium may slow prostate cancer tumor progression. Ongoing randomized trials of selenium supplements may help to further evaluate this issue. The premorbid level of selenoprotein P in plasma from subjects with cancer at different sites was compared with that from control subjects in a nested case-control study. A health screening of 12,500 middle-aged men was performed during 1974-1982 in Malmö, Sweden, and from the 400 cancer cases that were identified during follow-up until the end of 1988, 302 plasma samples were available for analysis of selenoprotein P. Two living controls per case of the same screening day and age were chosen. Selenoprotein P levels in subgroups of major cancer sites were lower in cases than in controls for the respiratory tract (1.20 and 1.30 arbitrary units, respectively; p < 0.05) cancer group. The odds ratio for overall cancer risk in the lowest quintile of selenoprotein P level compared with that in the highest was 5.2 [p (for trend) = 0.01]. In subgroups of major cancer sites, the odds ratios for cancer risk in the lowest tertile compared with the highest were 6.0 [p (for trend) = 0.004] in the respiratory tract and 3.4 [p (for trend) = 0.002] in the digestive tract. In cases + controls, selenoprotein P was lower in smokers than in nonsmokers (p < 0.05). Selenoprotein P was significantly correlated to plasma albumin, fasting blood glucose, and body mass index and inversely correlated to plasma alpha 1-antitrypsin and gamma-glutamyl transferase. The results suggest that a low plasma selenoprotein P level is associated with higher future risk of respiratory and digestive tract cancer in middle-aged men. The hypothesis that low selenium may in some circumstances be a risk factor for lung cancer was investigated in a case-control study nested within a longitudinal study. Serum samples from 9,101 cancer-free individuals were collected and stored at -20 degrees C by the Finnish Mobile Clinic in 1968-1971 and 1973-1976. During follow-up until the end of 1991, 95 cases of lung cancer were diagnosed. Selenium concentrations were determined from the serum samples of the cases and 190 controls, individually matched for sex, age, and place of residence. Mean levels of serum selenium in cases and controls were 53.2 microg/liter and 57.8 microg/liter, respectively. The relative risk of lung cancer between the highest and lowest tertiles of serum selenium, adjusted for smoking, serum alpha-tocopherol, serum cholesterol, serum copper, serum orosomucoid, and body mass index (kg/m2), was 0.41 (95% confidence interval (CI) 0.17-0.94). The association was stronger at lower levels (<5.9 mg/liter) of alpha-tocopherol (relative risk=0.24, 95% CI 0.07-0.85). The association was also pronounced among current smokers and at higher levels of serum orosomucoid and serum copper. The relative risk for smokers who were twice ranked in higher selenium tertiles, at an interval of 4-7 years, in comparison with smokers who remained in the lowest tertile was 0.16 (95% CI 0.04-0.74). In accordance with the hypothesis, the findings suggest that very low selenium status may contribute to the risk of lung cancer. Serum samples were collected in Hiroshima and Nagasaki, Japan, from 1970 to 1972 for 208 persons who in 1973-1983 developed stomach cancer; for 77 who in 1973-1983 developed lung cancer; and for controls matched for age, sex, city, and season of blood collection. Average serum levels of selenium and zinc were slightly (< 5%) but not significantly lower among the cancer cases than among controls. Smoking-adjusted risks of lung cancer were elevated only among those in the lowest quartiles of serum selenium [odds ratio (OR) = 1.8] and zinc (OR = 1.3); the trends in risk of this cancer with decreasing serum levels were neither linear nor significant. Little or no excess risk of stomach cancer was observed among those with lowest levels of selenium (OR = 1.0) or zinc (OR = 1.2). These exploratory findings add to limited data available from other reports showing slightly increased risks of lung cancer associated with low blood levels of selenium, but suggest little association with either lung or stomach cancer across normal selenium or zinc ranges in this Japanese population. We studied the relation of serum vitamin A (retinol), beta-carotene, vitamin E, and selenium to the risk of lung cancer, using serum that had been collected during a large blood-collection study performed in Washington County, Maryland, in 1974. Levels of the nutrients in serum samples from 99 persons who were subsequently found to have lung cancer (in 1975 to 1983) were compared with levels in 196 controls who were matched for age, sex, race, month of blood donation, and smoking history. A strong inverse association between serum beta-carotene and the risk of squamous-cell carcinoma of the lung was observed (relative odds, 4.30; 95 percent confidence limits, 1.38 and 13.41). Mean (+/- SD) levels of vitamin E were lower among the cases than the controls (10.5 +/- 3.2 vs. 11.9 +/- 4.90 mg per liter), when all histologic types of cancer were considered together. In addition, a linear trend in risk was found (P = 0.04), so that persons with serum levels of vitamin E in the lowest quintile had a 2.5 times higher risk of lung cancer than persons with levels in the highest quintile. These data support an association between low levels of serum vitamin E and the risk of any type of lung cancer and between low levels of serum beta-carotene and the risk of squamous-cell carcinoma of the lung. The association between the serum selenium level and the subsequent incidence of cancer was investigated in a longitudinal study of 39,268 men and women participating in the Social Insurance Institution's Mobile Clinic Health Examination Survey in Finland. The baseline examinations, including the collection of blood samples, were performed in 1968-1972. During a median follow-up of 10 years, 1,096 new cancer cases were identified from the files of the Finnish Cancer Registry. Selenium concentrations were measured from the stored serum samples collected from these cancer cases and from two controls per case, matched for sex, municipality, and age. The mean serum selenium level was 59.1 micrograms/L among all male cancer cases and 62.5 micrograms/L among controls. The difference was statistically significant (P less than .001). Corresponding values among women were 63.6 and 63.9 micrograms/L, respectively. Low serum selenium levels were associated with an increased risk of developing cancer at several sites, especially cancers of the stomach and lung among men. The relative risk of lung cancer between the highest and lowest decile of serum selenium was 0.11, and it differed significantly from unity (P less than .001). These findings are in agreement with the hypothesis that low selenium intake may increase the risk of some cancers among men. Although smoking is the primary risk factor for lung cancer, there is evidence to suggest that fruit and vegetable intake are important cofactors. The present case-control study, nested within the Multiethnic Cohort Study, examined the associations of biomarkers of fruit and vegetable intake (individual plasma micronutrient levels), serum selenium, and a urinary biomarker for total lipid peroxidation with lung cancer risk. Two hundred seven incident cases were matched to 414 controls on age, sex, ethnicity, study location (Hawaii or California), smoking status, date/time of collection, and hours of fasting. We measured prediagnositic circulating levels of individual tocopherols and carotenoids, retinol, and serum selenium, and urinary 15-isoprostane F(2t). Conditional logistic regression was used to compute odds ratios (OR) and 95% confidence intervals (CI). For men, strong reductions in risk were seen with increasing tertiles of each plasma carotenoid, with the ORs for the third tertile, compared with the first tertile, ranging from 0.24 to 0.45 (P(trends), 0.002-0.04). No associations were found among women for carotenoids or among either sex for tocopherols, selenium, and retinol. A doubling in risk was seen for men in the second and third tertiles, compared with the first tertile of urinary 15-isoprostane F(2t) (OR, 2.31; 95% CI, 1.02-5.25; and OR, 2.16; 95% CI, 0.98-4.78). This study supports the previously observed association between circulating carotenoids and lung cancer risk in men, and adds to the limited literature regarding urinary 15-isoprostane F(2t) as a marker of cancer risk. Future research examining the possible relationship between isoprostanes and lung cancer is warranted. Inadequate plasma selenium can adversely affect the maintenance of optimal health; therefore, reported decreases in plasma selenium in an aging population are cause for concern. To further examine this hypothesis, we explored the relationships between plasma selenium and mortality in an elderly population: the EVA (Etude du Vieillissement Artériel) study.
                The EVA study was a 9-year longitudinal study with 6 periods of follow-up. During the 2-year period from 1991 to 1993 (EVA0), 1389 men and women born between 1922 and 1932 were recruited. The effects of plasma selenium at baseline on mortality were determined by Cox proportional hazards regression analysis, adjusting for the following variables: sociodemographic characteristics, dietary habits, health, and cognitive factors.
                During the 9-year follow-up, 101 study participants died. Baseline plasma selenium was higher in individuals who were alive at the end of follow-up [mean (SD), 1.10 (0.20) micromol/L] than in those who died during the follow-up [1.01 (0.20) micromol/L; P <10(-4)]. Mortality rates were significantly higher in individuals with low selenium [increments = 0.2 micromol/L; relative risk (RR) = 1.56 (95% confidence interval, 1.28-1.89)]. After we controlled for various potential confounding factors, this association remained significant [RR = 1.54 (1.25-1.88)]. When the underlying causes of death were considered, we found an association with cancer-related mortality [adjusted RR = 1.79 (1.32-2.44)].
                Even if it is premature to present selenium as a longevity indicator in an elderly population, our results are in accordance those of large, interventional, randomized trials with selenium, which suggest that this essential trace element plays a role in health maintenance in aging individuals. Selenium is a potential chemopreventive agent against prostate cancer, whose chemoprotective effects are possibly mediated through the antioxidative properties of selenoenzymes. Interrelations with other antioxidative agents and oxidative stressors, such as smoking, are poorly understood.
                The aims were to investigate the association between serum selenium and prostate cancer risk and to examine interactions with other antioxidants and tobacco use.
                A nested case-control study was performed within the screening arm of the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Serum selenium in prospectively collected samples was compared between 724 incident prostate cancer case subjects and 879 control subjects, frequency-matched for age, time since initial screen, and year of blood draw. The men were followed for up to 8 y.
                Overall, serum selenium was not associated with prostate cancer risk (P for trend = 0.70); however, higher serum selenium was associated with lower risks in men reporting a high (more than the median: 28.0 IU/d) vitamin E intake [odds ratio (OR) for the highest compared with the lowest quartile of selenium: 0.58; 95% CI: 0.37, 0.91; P for trend = 0.05; P for interaction = 0.01] and in multivitamin users (OR for highest compared with the lowest quartile of selenium: 0.61; 95% CI: 0.36, 1.04; P for trend = 0.06; P for interaction = 0.05). Furthermore, among smokers, high serum selenium concentrations were related to reduced prostate cancer risk (OR for the highest compared with the lowest quartile of selenium: 0.65; 95% CI: 0.44, 0.97; P for trend = 0.09; P for interaction = 0.007).
                Greater prediagnostic serum selenium concentrations were not associated with prostate cancer risk in this large cohort, although greater concentrations were associated with reduced prostate cancer risks in men who reported a high intake of vitamin E, in multivitamin users, and in smokers. Prediagnostic selenium concentrations measured in archived toenails were inversely associated with bladder cancer risk in women (P for trend = 0.02), but not in men, in a nested case-control study of 338 cases and 341 matched controls. These findings may be due to chance and more studies are needed to determine whether associations between selenium and bladder cancer risk differ by sex. nan 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. The incidence of esophageal adenocarcinoma (EA) and its precursor condition, Barrett's esophagus, has risen rapidly in the United States for reasons that are not fully understood. Therefore, we evaluated the association between use of supplemental vitamins and minerals and risk of neoplastic progression of Barrett's esophagus and EA. The Seattle Barrett's Esophagus Program is a prospective study based on 339 men and women with histologically confirmed Barrett's esophagus. Participants underwent baseline and periodic follow-up exams, which included endoscopy and self-administered questionnaires on diet, supplement use, and lifestyle characteristics. Use of multivitamins and 4 individual supplements was calculated using time-weighted averages of reported use over the observational period. Cox proportional-hazards models were used to calculate hazard ratios (HR) for each endpoint: EA, tetraploidy, and aneuploidy. During a mean follow-up of 5 yr, there were 37 cases of EA, 42 cases of tetraploidy, and 34 cases of aneuploidy. After controlling for multiple covariates including diet, nonsteroidal anti-inflammatory drug use, obesity, and smoking, participants who took 1 or more multivitamin pills/day had a significantly decreased risk of tetraploidy [HR = 0.19; 95% confidence interval (CI) = 0.08-0.47) and EA (HR = 0.38; 95% CI = 0.15-0.99] compared to those not taking multivitamins. Significant inverse associations were also observed between risk of EA and supplemental vitamin C (> or = 250 mg vs. none: HR = 0.25; 95% CI = 0.11-0.58) and vitamin E (> or = 180 mg vs. none: HR = 0.25; 95% CI = 0.10-0.60). In this cohort study, use of multivitamins and single antioxidant supplements was associated with a significantly reduced risk of EA and markers of neoplastic progression among individuals with Barrett's esophagus. To examine whether antioxidant supplement use is associated with melanoma risk in light of recently published data from the Supplementation in Vitamins and Mineral Antioxidants (SUVIMAX) study, which reported a 4-fold higher melanoma risk in women randomized to receive a supplement with nutritionally appropriate doses of antioxidants.
                Population-based prospective study (Vitamins and Lifestyle [VITAL] cohort).
                Western Washington State.
                A total of 69 671 men and women who self-reported (1) intake of multivitamins and supplemental antioxidants, including selenium and beta carotene, during the past 10 years and (2) melanoma risk factors on a baseline questionnaire. Main Outcome Measure Incident melanoma identified through linkage to the Surveillance, Epidemiology, and End Results (SEER) cancer registry.
                Cox proportional hazards regression models were used to estimate multivariable relative risks (RRs) and 95% confidence intervals (CIs) for multivitamin, supplemental selenium, and supplemental beta carotene use. After adjusting for melanoma risk factors, we did not detect a significant association between multivitamin use and melanoma risk in women (RR, 1.14; 95% CI, 0.78-1.66) or in men (RR, 1.09; 95% CI, 0.83-1.43). Moreover, we did not observe increased melanoma risk with the use of supplemental beta carotene (RR, 0.87; 95% CI, 0.48-1.56) or selenium (RR, 0.98; 95% CI, 0.69-1.41) at doses comparable with those of the SUVIMAX study. Conclusion Antioxidants taken in nutritional doses do not seem to increase melanoma risk. Selenium levels in serum samples collected in 1973 from 111 subjects in whom cancer developed during the subsequent 5 years were compared with those in serum samples from 210 cancer-free subjects matched for age, race, sex, and smoking history. The mean selenium level of cases (0.129 +/- SEM 0.002 micrograms/ml) was significantly lower than that of controls (0.136 +/- 0.002 micrograms/ml). The risk of cancer for subjects in the lowest quintile of serum selenium was twice that of subjects in the highest. Multivariate adjustment for geographical area and serum levels of lipids, vitamins A and E, and carotene, did not alter this relation. The association between low selenium level and cancer was strongest for gastrointestinal and prostatic cancers. Serum levels of vitamins A and E compounded the effect of low selenium; relative risks for the lowest tertile of selenium were 2.4 and 3.9 in the lowest tertiles of vitamins E and A, respectively. Selenium, an essential trace element involved in defense against oxidative stress, may prevent cancer and cardiovascular disease. We evaluated the association between selenium levels and all-cause and cause-specific mortality in a representative sample of US adults.
                Serum selenium levels were measured in 13,887 adult participants in the Third National Health and Nutrition Examination Survey. Study participants were recruited from 1988 to 1994 and followed up for mortality for up to 12 years.
                The mean serum selenium level was 125.6 ng/mL. The multivariate adjusted hazard ratios comparing the highest (> or = 130.39 ng/mL) with the lowest (< 117.31 ng/mL) serum selenium level tertile were 0.83 (95% confidence interval [CI], 0.72-0.96) for all-cause mortality, 0.69 (95% CI, 0.53-0.90) for cancer mortality, and 0.94 (95% CI, 0.77-1.16) for cardiovascular mortality. However, based on spline regression models, the association between serum selenium levels and all-cause and cancer mortality was nonlinear, with an inverse association at low selenium levels (< 130 ng/mL) and a modest increase in mortality at high selenium levels (> 150 ng/mL). There was no association between serum selenium levels and cardiovascular mortality.
                In a representative sample of the US population, we found a nonlinear association between serum selenium levels and all-cause and cancer mortality. Increasing serum selenium levels were associated with decreased mortality up to 130 ng/mL. Our study, however, raises the concern that higher serum selenium levels may be associated with increased mortality. Epidemiological studies have suggested that low levels of selenium are associated with a higher incidence of both lung and prostate cancer. We analyzed the selenium serum concentration in 356 Carotene and Retinol Efficacy Trial (CARET) participants who later developed lung cancer and 356 matched controls and in 235 prostate cancer cases and 456 matched controls. Serum samples were obtained a mean of 4.7 years before diagnosis for both tumor types. Controls were matched to cases by year of randomization, age, smoking status, treatment arm, exposure population (asbestos workers or cigarette smokers), and year of blood draw. In the control population (n = 820), significant predictors of low serum selenium concentration were current smoking status and East Coast locations of the study center. Overall, there was no significant difference in mean serum selenium in lung cancer cases versus controls (11.91 microg/dl versus 11.77 microg/dl) or prostate cancer cases versus controls (11.48 microg/dl versus 11.43 microg/dl). No statistically significant trend in odds ratio was seen across quartiles of serum selenium for lung cancer (P = 0.49) or prostate cancer (P = 0.69). In a subpopulation of 174 prostate cancer patients who had clinical and pathological staging material reviewed, there was no association between serum selenium and Gleason score or clinical or pathological stage. In the CARET population of current and former smokers consuming an ad libitum diet, the serum concentration of selenium was not a risk factor for either lung cancer or prostate cancer. To study the preventive effects of selenium on primary liver cancer.
                After screening of blood samples in 18,000 males from 20 to 65 years-old in Qidong, Jiangsu province (a high risk area for liver cancer), 2,065 cases of HBsAg positive, AFP negative and normal liver function (normal ALT values) were found. The subjects were randomly divided into two groups, based on their residence areas; 1,112 subjects (experimental group) received one tablet of sodium selenite (0.5 mg Se) every day and 953 subjects (control group) received one placebo tablet every day.
                During three years of intervention and follow up, the blood selenium concentration and glutathione peroxidase activity of the subjects in the experimental group were increased and had significant difference as compared with those of the control group (P < 0.01). At the same time, the prevalence rate of micronucleus cells in peripheral blood lymphocytes in the experimental group was significantly lower than that of the control group (P < 0.01), and the incidence of new liver cancer in the experimental group (3 057.55/10(6), 34 cases out of 1,112 subjects) was significantly lower than the control group (5 981.11/10(6); 57 cases out of 953 subjects) (P < 0.01).
                The results confirms that selenium supplementation in general populations lived in high risk is effective in the prevention of liver cancer and the using of selenium tablets is simple and feasible. nan To determine the possible role of selenium in the pathogenesis of breast cancer, prediagnostic Se 77 m isotope levels in toenail clippings in premenopausal women were measured. The study was designed as a case-referent study nested in a cohort. Participants were recruited from the DOM-project breast-cancer screening cohorts. No decreased selenium levels were found up to two years prior to diagnosis, nor were Se levels different between prevalent and/or incident breast cancer cases, referents and women with benign breast disease. Se levels measured in nails could not detect women at higher risk for breast cancer. This study does not support the idea that Se supplementation could have a preventive potential for premenopausal breast cancer in women in the Netherlands. To evaluate the association of prediagnostic serum antioxidants and lung cancer risk we conducted a case-control study nested in an occupational cohort of tin miners.
                Male workers free of cancer enrolled in the cohort. During up to 6 years of follow-up, 339 lung cancer cases were diagnosed and, among these cases, those who donated blood prospectively (n = 108) were eligible for this study. For each case, two controls alive and free of cancer at the time of case diagnosis were matched on age and date of blood collection.
                Overall, we observed no association between serum alpha-tocopherol, gamma-tocopherol or selenium levels and lung cancer risk. However, a significant gradient of decreasing lung cancer risk with increasing serum alpha-tocopherol was apparent for men less than 60 years old (odds ratio by tertile: 1.0, 0.9, 0.2; trend p = 0.002). Alpha-tocopherol was also protective in men who reported no alcohol drinking (OR by tertile: 1.0, 0.6, 0.3; trend p = 0.008).
                Although there were no significant overall associations between prospectively collected serum alpha-tocopherol, gamma-tocopherol or selenium and incidence of lung cancer, results from this study suggest that higher alpha-tocopherol levels may be protective in men less than 60 years old and in those who do not drink alcohol. High rates of hepatitis B virus (HBV) infection and primary liver cancer (PLC) are present in Qidong county. Epidemiological surveys demonstrated an inverse association between selenium (Se) level and regional cancer incidence, as well as HBV infection. Four-year animal studies showed that dietary supplement of Se reduced the HBV infection by 77.2% and liver precancerous lesion by 75.8% of ducks, caused by exposure to natural environmental etiologic factors. An intervention trial was undertaken among the general population of 130,471. Individuals in five townships were involved for observation of the preventive effect of Se. The 8-yr follow-up data showed reduced PLC incidence by 35.1% in selenized table salt supplemented vs the nonsupplemented population. On withdrawal of Se from the treated group, PLC incidence rate began to increase. However, the inhibitory response to HBV was sustained during the 3-yr cessation of treatment. The clinical study among 226 Hepatitis B Surface Antigen (HBsAg)-positive persons provided either 200 micrograms of Se in the form of selenized yeast tablet or an identical placebo of yeast tablet daily for 4 yr showed that 7 of 113 subjects were diagnosed as having PLC in the placebo group, whereas no incidence of PLC was found in 113 subjects supplemented with Se. Again on cessation of treatment, PLC developed at a rate comparable to that in the control group, demonstrating that a continuous intake of Se is essential to sustain the chemopreventive effect. In a population study, 10,000 men (aged 46-48 years) were invited to a health screening program. At follow-up, which was up to eight years later, 61 subjects had died from cancer; from 35 of these subjects, plasma samples were available that were obtained at the initial screening. These samples, together with samples from two living controls for each case, were analyzed for selenium, retinol, cholesterol, triglyceride, and a number of plasma proteins. Plasma selenium was significantly lower (p less than 0.05) in cases than in controls (means: 1.06 vs. 1.12 mumol/l). The proportion of cases increased significantly from the highest to the lowest quintile of plasma selenium, and the relative risk for cancer death was 3.8 times higher in the lowest quintile compared with the highest. Mean plasma retinol was similar in cases (2.53 mumol/l) and controls (2.56 mumol/l). Cases and controls also had similar values for plasma cholesterol, triglyceride, uric acid, apolipoprotein B, orosomucoid, prealbumin, retinol-binding protein, and beta 2-microglobulin. Apolipoprotein AI in plasma was lower among cases (p less than 0.025). Cases smoked significantly more than controls did (p less than 0.05). Data indicate that low plasma selenium was a risk factor for cancer death in middle-aged men who lived in the same area. Further studies are necessary to establish whether differences in selenium intake, selenium metabolism, or other factors related to selenium are responsible for the relations observed. At present, the available data do not justify selenium supplementation programs in the whole population. The purpose of this study was to evaluate the effect of selenium (Se) in the prevention of human primary liver cancer. Three intervention trials were conducted among the residents at high risk to primary liver cancer (PLC) in Qidong county, Jiang-su province, the People's Republic of China. This area has the second highest rate of PLC in China. One trial was undertaken among the general population in a township with supplement of table salt fortified with 15 ppm anhydrous sodium selenite (Se-salt) for 5 y and the other four townships with similar PLC incidence rate served as the controls using normal table salt. The second trial was undertaken among hepatitis B virus surface antigen carriers (HBVsAg+) receiving supplement of 200 micrograms Se in form of selenized yeast (Se-yeast) daily vs placebo for 4 y. The third trial was carried out in members of families with high PLC incidence using Se-yeast (200 micrograms of Se daily) vs placebo for 2 y. The results showed that nutritional supplement of Se could reduce the PLC incidence significantly. The association between serum selenium concentration and risk of cancer was studied in a nested case control study. Case control pairs came from a population of 9364 people examined in 1979. During the six year follow up, 60 men and women aged between 20-54 at the time of blood sampling, who had been free of malignant disease, developed cancer. The mean serum selenium concentration of 1.56 mumol/l (123.2 micrograms/l) in patients was not significantly different from that in controls (1.63 mumol/l (128.7 micrograms/l]. The difference in mean selenium concentration was largest and most significant for haematological malignancies alone. The difference in selenium concentrations in cases of fatal cancer compared with controls was significant (p less than 0.01). The risk of developing adenocarcinomas does not seem to be influenced by serum selenium concentration. A nested case-control study was conducted to assess the relation between serum levels of selenium and retinol and the subsequent risk of cancer. During the years 1972-1984, in northwest Washington State, 156 cases of cancer were identified among members of two employee cohorts from whom specimens had been previously obtained and stored. Two hundred eighty-seven controls were selected from these cohorts and matched to cases on the basis of employer, age, sex, race, and date of blood draw. Selenium and retinol levels were measured by neutron activation and high pressure liquid chromatography, respectively. Information on known cancer risk factors was collected by telephone interviews of subjects and next of kin. Levels of selenium and retinol were unassociated with the incidence of cancer of all sites combined, both overall and within subgroups defined by age, sex, levels of the other micronutrient, time between blood draw and diagnosis, smoking status, and family history of cancer. These findings suggest that neither serum levels of selenium nor those of retinol have an appreciable effect on the risk of cancer. Selenium (Se) is an essential trace mineral with known anticarcinogenic properties in humans. However, few studies have examined the association between Se nutrient status and risk of liver cancer. We conducted a nested case-control study comparing the Se content in toenail clippings of 166 individuals (154 men, 12 women) with hepatocellular carcinoma (HCC) to 394 healthy controls (360 men, 34 women) in Haimen City, China, where HCC is a leading cause of mortality. Toenail Se concentration was measured by inductively coupled plasma-optical emission spectroscopy. Median toenail Se was lower for HCC cases than controls (p = 0.03). Adjusted odds ratios and 95% confidence intervals for HCC mortality by increasing quartile of toenail Se were 1.00 (reference), 0.58 (0.32-1.03), 0.83 (0.48-1.42) and 0.50 (0.28-0.90), with a marginally significant trend in risk observed (p for trend = 0.06). This inverse association appeared stronger among those who did not consume alcohol and among women. Future studies are needed to examine the interrelationship between Se, viral hepatitis infection and HCC in order to better understand the etiologic mechanisms involved and evaluate the true chemopreventive potential of Se compounds for liver diseases.
                Copyright 2005 Wiley-Liss, Inc. Antioxidant nutrients and carotenoids have been inconsistently associated with ovarian cancer risk. We examined the relationship between intake of dietary and supplemental antioxidant nutrients including vitamins C, E, and selenium as well as carotenoids and vitamin A and ovarian cancer in 133,614 postmenopausal women enrolled in the Women's Health Initiative (WHI) study. Dietary intake was assessed using a food frequency questionnaire, and ovarian cancer endpoints were centrally adjudicated. Cox regression models were used to estimate the risk for invasive ovarian cancer in relation to each of the antioxidant nutrients and carotenoids under consideration using models stratified for a WHI study component. A total of 451 cases of invasive ovarian cancer were diagnosed over 8.3 yr of follow-up. Dietary intake at baseline was not significantly different for cases vs. controls. Cases reported greater intake of supplemental vitamin C (358.0 mg/day vs. 291.6 mg/day, respectively; P = 0.024). Multivariate modeling (P for trend) of the risk for developing ovarian cancer did not suggest any significant relationships among dietary factors and ovarian cancer risk. The results from this prospective study of well-nourished, postmenopausal women suggest that intake of dietary antioxidants, carotenoids, and vitamin A are not associated with a reduction in ovarian cancer risk. Both experimental and epidemiologic studies have linked a low dietary intake of selenium with an increased risk of cancer. The authors examined the association between plasma selenium levels and risk of hepatocellular carcinoma (HCC) among chronic carriers of hepatitis B and/or C virus in a cohort of 7,342 men in Taiwan who were recruited by personal interview and blood draw during 1988-1992. After these men were followed up for an average of 5.3 years, selenium levels in the stored plasma were measured by using hydride atomic absorption spectrometry for 69 incident HCC cases who were positive for hepatitis B surface antigen (HBsAg) and/or antibodies against hepatitis C virus (mostly HBsAg positive) and 139 matched, healthy controls who were HBsAg positive. Mean selenium levels were significantly lower in the HCC cases than in the HBsAg-positive controls (p = 0.01). Adjusted odds ratios of HCC for subjects in increasing quintiles of plasma selenium were 1.00, 0.52, 0.32, 0.19, and 0.62, respectively. The inverse association between plasma selenium levels and HCC was most striking among cigarette smokers and among subjects with low plasma levels of retinol or various carotenoids. There was no clear evidence for an interaction between selenium and alpha-tocopherol in relation to HCC risk. The association of serum selenium with the subsequent risk of death from cancer was investigated in a case-control study that was nested in a prospective nine-year follow-up study in the Netherlands. In 1975-1978, 10,532 persons in the Dutch town of Zoetermeer who were aged five years or more participated in a medical survey. Serum samples were collected and stored at -20 C. For the 82 persons who died of cancer since the baseline examination, 164 cohort members still alive by the end of 1983 were selected as controls and matched for age, sex, and smoking. Cancer deaths that occurred in the first year of follow-up were excluded, leaving 69 cases for statistical analyses. The mean serum selenium level of 116.7 +/- 4.0 micrograms/liter among male cancer deaths (n = 40) was significantly different (p = 0.04) from that in the control subjects (126.4 +/- 3.1 micrograms/liter). In females, selenium levels were similar among cases and controls. The adjusted risk of death from cancer for men in the lowest quintile of serum selenium (below 100.8 micrograms/liter) was more than twice that of subjects with higher levels (relative risk = 2.7,90% confidence interval = 1.2-6.2). These data support recent findings of an increased cancer risk associated with low serum selenium levels in men but not in women.
No reliable conclusions can be drawn regarding a causal relationship between low selenium exposure and an increased risk of cancer. Despite evidence for an inverse association between selenium exposure and the risk of some types of cancer, these results should be interpreted with care due to the potential limiting factors of heterogeneity and influences of unknown biases, confounding and effect modification.
The effect of selenium supplementation from RCTs yielded inconsistent results. To date, there is no convincing evidence that selenium supplements can prevent cancer in men, women or children.