Purpose
This study was conducted to investigate the effect of Se supplementation on prostate cancer incidence in men at high risk for prostate cancer.
Methods
A Phase 3 randomized, double-blind, placebo-controlled clinical trial was conducted in 699 men at high risk for prostate cancer (prostate specific antigen (PSA) >4 ng/ml and/or suspicious digital rectal examination and/or PSA velocity >0.75ng/ml/year), but with a negative prostate biopsy. Participants were randomized to receive daily oral placebo (N = 232), 200 µg selenium (N =234), or 400 µg selenium (N=233) as selenized yeast. They were followed every six months for up five years. The time to diagnosis of prostate cancer was compared between treatment groups using the Cox-proportional hazards model.
Result
Compared to placebo, the hazard ratios [95% confidence intervals] for risk of developing prostate cancer in the selenium 200 µg/day or the selenium 400 µg/day group were 0.94 [0.52, 1.7] and 0.90 [0.48, 1.7] respectively. PSA velocity in the selenium arms was not significantly different from that observed in the placebo group (p=0.18 and p=0.17, respectively).
Conclusion
Selenium supplementation appeared to have no effect on the incidence of prostate cancer in men at high risk. In conjunction with results of other studies, these data indicate that selenium supplementation may not have a role in prostate cancer chemoprevention.
Infection after flexible cystoscopy is rare and not associated with significant morbidity. A much larger study would be required to determine whether antibiotic prophylaxis significantly reduces the rate of postprocedure UTI.
Cancer cachexia may be mediated by endogenous peptides such as tumour necrosis factor alpha (TNF-alpha). Insulin resistance occurs in these patients, and is also seen experimentally with TNF-alpha administration. In this study, insulin sensitivity and energy metabolism were measured in 11 patients with gastrointestinal cancer and ten controls, using the euglycaemic glucose clamp and indirect calorimetry. Patients with cancer were significantly more insulin resistant than controls (P < 0.01) and in such patients insulin resistance correlated with serum TNF-alpha level (rs = 0.74, P < 0.01). Fasting insulin levels also correlated inversely with insulin sensitivity (rs = -0.62, P = 0.003). These results suggest a possible association between endogenous TNF-alpha production and insulin resistance in patients with gastrointestinal cancer.
The study provides data relating serum selenium concentration to activities of 2 key selenoenzymes, hemolysate thioredoxin reductase (TR) and glutathione peroxidase (GPx), measured by spectrophotometry, in a group of men at high risk for prostate cancer. This trial enrolled 43 patients with elevated prostate-specific antigen but negative biopsy for prostate cancer. Such individuals have a high risk of developing prostate cancer in the succeeding 5 y. In the men with baseline serum selenium concentrations ranging from 0.74-1.62 micromol/L (59-128 microg/L), hemolysate TR (r = 0.359, P < 0.05) and GPx (r = 0.341, P < 0.05) activities increased with increasing serum selenium. Furthermore, after a run-in period of 1 mo, men participated in a randomized, double-blind, placebo-controlled selenium supplementation trial for 6 mo and received a placebo, or 200 or 400 microg of Se per day, in the form of a seleno yeast. This study is a subsidiary of an ongoing Phase III cancer chemoprevention trial and, as such, randomization groups have not yet been revealed. After 6 mo of being on trial and with an estimated 66% of the group being supplemented with seleno yeast, the TR activity of the group increased by 80% relative to baseline. In contrast, 6 mo of selenium supplementation did not affect GPx activity. This study presents, to our knowledge for the first time, both measurements of human hemolysate TR activity and its relation to serum selenium.
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