Duffield-Lillico et al. (1) recently updated cancer incidence estimates among patients with nonmelanoma skin cancer randomized to receive either 200 μg/die (organic?) selenium as selenized yeast or placebo. They reported that an increase of only 25 months of follow-up attenuated the previously reported reduction in incidence of prostate, colorectal, and lung cancer (2). This finding is consistent with the hypothesis that a favorable effect of selenium administration, if there is any, is short term. Furthermore, the reduction appears to be confined to males and subjects with the lowest selenium status at baseline. In contrast, there were excesses for some other cancer sites, including breast cancer, melanoma, head and neck cancer, lymphoma and leukaemia, confirming earlier epidemiologic reports (3, 4, 5, 6). In view of this uncertain benefit, it may be prudent to reserve additional testing (7) to patients with frank cancer. Additional follow-up from this experimental cohort beyond the end of the active intervention (which ended on February 1, 1996) would be of great interest.
Duffield-Lillico et al. (1) also reported an excess cancer risk in selenium-treated patients who had the highest plasma selenium levels at baseline. It would be interesting to know which site-specific cancers showed this relation with baseline selenium levels.
Finally, this trial may offer unique opportunities to examine the possible occurrence of toxic effects of selenium in humans (8, 9). Recent clinical and epidemiologic studies indicated that both the possible effects short term (decrease of triiodothyronine synthesis and of natural killer cell activity) and long term (such as motor neurons toxicity) may occur at much low levels of selenium exposure, although the chemical forms of selenium may be a determining factor for these effects (10). Should biological specimens after the beginning of selenium treatment be available from cohort members and should a follow-up extended to other degenerative diseases such as amyotrophic lateral sclerosis be possible, extensive investigation of the above-mentioned issue would be of great interest.
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