Objective
To test if supplemental dietary selenium is associated with changes in the incidence of prostate cancer.
Patients and method
A total of 974 men with a history of either a basal cell or squamous cell carcinoma were randomized to either a daily supplement of 200 μg of selenium or a placebo. Patients were treated for a mean of 4.5 years and followed for a mean of 6.5 years.
Results
Selenium treatment was associated with a significant (63%) reduction in the secondary endpoint of prostate cancer incidence during 1983–93. There were 13 prostate cancer cases in the selenium‐treated group and 35 cases in the placebo group (relative risk, RR=0.37, P=0.002). Restricting the analysis to the 843 patients with initially normal levels of prostate‐specific antigen (≤4 ng/mL), only four cases were diagnosed in the selenium‐treated group and 16 cases were diagnosed in the placebo group after a 2 year treatment lag, (RR=0.26 P=0.009). There were significant health benefits also for the other secondary endpoints of total cancer mortality, and the incidence of total, lung and colorectal cancer. There was no significant change in incidence for the primary endpoints of basal and squamous cell carcinoma of the skin. In light of these results, the ‘blinded’ phase of this trial was stopped early.
Conclusions
Although selenium shows no protective effects against the primary endpoint of squamous and basal cell carcinomas of the skin, the selenium‐treated group had substantial reductions in the incidence of prostate cancer, and total cancer incidence and mortality that demand further evaluation in well‐controlled prevention trials.
effects of treatment overall and within subgroups of baseline prostate-specific antigen (PSA) and plasma selenium concentrations were examined using incidence rate ratios and Cox proportional hazards models.
RESULTSSS continued to significantly reduce the overall incidence (relative risk and 95% confidence interval) of prostate cancer (0.51, 0.29-0.87). The protective effect of SS appeared to be confined to those with a baseline PSA level of £ 4 ng/mL (0.35, 0.13-0.87), although the interaction of baseline PSA and treatment was not statistically significant. Participants with baseline plasma selenium concentrations only in the lowest two tertiles (< 123.2 ng/mL) had significant reductions in prostate cancer incidence. A significant interaction between baseline plasma selenium and treatment was detected.
CONCLUSIONTo the end of the blinded treatment the NPC trial continued to show a significant protective effect of SS on the overall incidence of prostate cancer, although the effect was restricted to those with lower baseline PSA and plasma selenium concentrations.
An easy-to-implement global procedure for testing the four assumptions of the linear model is proposed. The test can be viewed as a Neyman smooth test and it only relies on the standardized residual vector. If the global procedure indicates a violation of at least one of the assumptions, the components of the global test statistic can be utilized to gain insights into which assumptions have been violated. The procedure can also be used in conjunction with associated deletion statistics to detect unusual observations. Simulation results are presented indicating the sensitivity of the procedure in detecting model violations under a variety of situations, and its performance is compared with three potential competitors, including a procedure based on the Box-Cox power transformation. The procedure is demonstrated by applying it to a new car mileage data set and a water salinity data set that has been used previously to illustrate model diagnostics.
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