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Selenium and vitamin E micronutrients have been advocated for the prevention of colorectal cancer. Colorectal adenoma occurrence was used as a surrogate for colorectal cancer in an ancillary study to the Selenium and Vitamin E Cancer Prevention Trial (SELECT) for prostate cancer prevention. The primary objective was to measure the effect of selenium (as selenomethionine) on colorectal adenomas occurrence, with the effect of vitamin E (as α-tocopherol) supplementation on colorectal adenoma occurrence considered as a secondary objective. Participants who underwent lower endoscopy while in SELECT were identified from a subgroup of the 35,533 men randomized in the trial. Adenoma occurrence was ascertained from the endoscopy and pathology reports for these procedures. Relative Risk (RR) estimates and 95% confidence intervals (CI) of adenoma occurrence were generated comparing those randomized to selenium versus placebo and to vitamin E versus placebo based on the full factorial design. Evaluable endoscopy information was obtained for 6,546 participants, of whom 2,286 had 1+ adenomas. Apart from 21 flexible sigmoidoscopies, all the procedures yielding adenomas were colonoscopies. Adenomas occurred in 34.2% and 35.7%, respectively, of participants whose intervention included or did not include selenium. Compared with placebo, the RR for adenoma occurrence in participants randomized to selenium was 0.96 (95% CI, 0.90-1.02; P = 0.194). Vitamin E did not affect adenoma occurrence compared with placebo (RR = 1.03; 95% CI, 0.96-1.10; P = 0.38). Neither selenium nor vitamin E supplementation can be recommended for colorectal adenoma prevention. Cancer Prev Res; 10(1); 45-54. ©2016 AACR., (©2016 American Association for Cancer Research.)

Epidemiologic and laboratory studies indicate that dietary selenium protects against prostate cancer. Results from clinical trials suggest that selenium-enriched yeast (SY) but not selenomethionine (SeMet) may be effective at reducing prostate cancer risk. Our objectives were to directly compare for the first time the effects of SeMet and SY on prostate cancer relevant biomarkers in men. We performed a randomized double blind, placebo-controlled trial of SY (200 or 285 μg/day) and SeMet (200 μg/day) administered for 9 months in 69 healthy men. Primary endpoints included blood levels of selenium-containing compounds and oxidative stress biomarkers [urine 8-hydroxy-2'-deoxyguanosine (8-OHdG) and 8-iso-prostaglandin-F2α (8-iso-PGF2α) and blood glutathione (GSH)]. Secondary endpoints included plasma glucose and PSA levels. Compliance was high in all groups (>95%). Plasma selenium levels were increased 93%, 54%, and 86% after 9 months in SeMet and low- and high-dose SY groups, respectively, and returned to baseline levels after a 3-month washout (P < 0.05). Levels of 8-OHdG and 8-iso-PGF2α were decreased 34% and 28%, respectively, after 9 months in the high-dose SY group (P < 0.05). These decreases were greatest in individuals with low baseline plasma levels of selenium (<127 ng/mL). No changes in serum PSA or blood glucose and GSH were observed. Overall, we showed for the first time, reductions in biomarkers of oxidative stress following supplementation with SY but not SeMet in healthy men. These findings suggest that selenium-containing compounds other than SeMet may account for the decrease in oxidative stress., (©2014 American Association for Cancer Research.)

Chemopreventive effects of the essential trace element selenium against prostate cancer have been shown in preclinical models and human observational studies, but results from clinical trials have been disappointing. It appears that there is a threshold selenium (Se) status below which improvement will decrease prostate cancer risk, but above which supplemental Se may be deleterious. Different forms of selenium have different effects, and genetic and other factors modify selenium's chemopreventive potential. Identification of men most likely to benefit from Se status improvement could have significant public health benefits., (©2014 American Association for Cancer Research.)

To evaluate the potential efficacy of selenium and vitamin E as inhibitors of prostate carcinogenesis, four chemoprevention studies using a common protocol were done in a rat model of androgen-dependent prostate cancer. After stimulation of prostate epithelial cell proliferation by a sequential regimen of cyproterone acetate followed by testosterone propionate, male Wistar-Unilever rats received a single i.v. injection of N-methyl-N-nitrosourea (MNU) followed by chronic androgen stimulation via subcutaneous implantation of testosterone pellets. At 1 week post-MNU, groups of carcinogen-treated rats (39-44/group) were fed either a basal diet or a basal diet supplemented with l-selenomethionine (3 or 1.5 mg/kg diet; study 1), dl-alpha-tocopherol (vitamin E, 4,000 or 2,000 mg/kg diet; study 2), l-selenomethionine + vitamin E (3 + 2,000 mg/kg diet or 3 + 500 mg/kg diet; study 3), or selenized yeast (target selenium levels of 9 or 3 mg/kg diet; study 4). Each chemoprevention study was terminated at 13 months post-MNU, and prostate cancer incidence was determined by histopathologic evaluation. No statistically significant reductions in prostate cancer incidence were identified in any group receiving dietary supplementation with selenium and/or vitamin E. These data do not support the hypotheses that selenium and vitamin E are potent cancer chemopreventive agents in the prostate, and when considered with the recent clinical data reported in the Selenium and Vitamin E Cancer Prevention Trial (SELECT), show the predictive nature of this animal model for human prostate cancer chemoprevention.

Previous epidemiologic observational and experimental studies investigated the potential of antioxidant micronutrients to modulate cancer risk, but these studies produced inconsistent results. In this pilot, randomized, double-blind, placebo-controlled clinical trial (n = 47), we assessed the effects of an antioxidant micronutrient combination (800 mg dl-alpha-tocopherol acetate, 24 mg beta-carotene, 1.0 g vitamin C, 200 microg l-selenomethionine, 7.2 mg riboflavin, 80 mg niacin, 60 mg zinc, 5 mg manganese) given daily over 4 months on oxidative and inflammatory biomarkers in patients with a history of sporadic colorectal adenoma. Plasma tumor necrosis factor-alpha (TNF-alpha), interleukin-6, and F2-isoprostane concentrations were measured using ELISAs, and cystine (CySS) was measured using high-performance liquid chromatography. Plasma TNF-alpha concentration decreased in the active treatment group by 37% relative to the placebo group (P = 0.002), and CySS decreased by 19% (P = 0.03); however, interleukin-6 and F2-isoprostane concentrations decreased in antioxidant-treated nonsmokers but increased in smokers, although these findings were not statistically significant. The decreases of TNF-alpha and CySS were more pronounced in nonsmokers. These data suggest that (a) an antioxidant micronutrient cocktail can modulate biomarkers of oxidative stress and inflammation in humans and (b) the effects of antioxidant micronutrient supplementation on biomarkers of inflammation and oxidative stress may differ according to smoking status.

The relative effectiveness of either sodium selenite or selenomethionine in the inhibition of mammary carcinogenesis was studied in virgin female Sprague-Dawley rats. In one experiment, rats were given 50 mg of 1-methyl-1-nitrosourea per kg of body weight s.c. at 50 days of age. Beginning 7 days post-1-methyl-1-nitrosourea, they were assigned to a basal diet containing 0.1 ppm of selenium or basal diet supplemented to contain either 4, 5, or 6 ppm of selenium as sodium selenite or 5 or 6 ppm of selenium as selenomethionine. Selenium treatment was continued until termination of the study 135 days after 1-methyl-1-nitrosourea treatment. Sodium selenite, at the 5-ppm level, was the most effective chemopreventive agent. The highest level of selenomethionine (6 ppm) caused grossly apparent liver damage. No liver damage was noted in sodium selenite-treated rats. In a second experiment, rats were given 5 mg of 7,12-dimethylbenz(a)anthracene at 50 days of age. Beginning 7 days after 7,12-dimethylbenz(a)anthracene treatment, rats were assigned randomly to the control group or to one of two selenium treatment groups receiving either 3.4 ppm of selenium as sodium selenite or 3.4 ppm as selenomethionine in their drinking water. Selenium supplementation was continued throughout the study until its termination at 111 days postcarcinogen . Sodium selenite significantly reduced cancer incidence and the average number of cancers per rat. Treatment with selenomethionine was less effective and caused severe liver damage. Although both sodium selenite and selenomethionine can inhibit some aspect of the postinitiation stage(s) of mammary carcinogenesis, selenium provided as sodium selenite was the more effective and less toxic of the two chemicals. Increasing the dose of sodium selenite above 5 ppm did not enhance the inhibitory activity of selenium.