The study began in l983 and included a total of 1,312 skin cancer
patients with a mean age of 63 seen at seven dermatology clinics
in the eastern United States. At that time, the primary purpose
of the study was to see if dietary supplements of selenium could
lower the incidence of basal cell or squamous cell skin cancers.
In 1990, secondary end points, including incidence of the most commonly
occurring cancers, lung, prostate, and colorectal were added.
"The results of this study are exciting because they show the
cancer prevention potential of a nutritional supplement to a normal
diet," said Larry C. Clark, Ph.D., MPH, associate professor of epidemiology
at the Arizona Cancer Center in Tucson, Ariz., and principal investigator
of the study. "The study needs to be repeated in other populations
before a public health recommendation can be made for selenium supplementation."
Patients in the double-blinded (neither patients nor doctors knew
who was receiving the intervention), randomized study took a tablet
containing 200 micrograms (ug) of selenium as brewer's yeast, or
placebo, daily for 4.5 years and were followed for an additional
6.4 years. Three-quarters of the patients were men. The trial ended
in January 1996, two years before the planned end of the trial.
American diets generally include enough grain, meat, and fish, the
primary sources of selenium, to meet the recommended dietary allowance
(RDA), 70 ug/day for men and 55 ug/day for women. (Although the
EPA established a reference dose, 350 ug/day, as a measure of the
maximum safe intake, the human toxicity levels for selenium have
not been definitely established.)
The study population, however, was from a region of the eastern
United States with relatively low selenium levels in soils and crops,
and before treatment had a mean plasma selenium concentration in
the lower range of the U.S. levels. The supplements increased the
plasma concentration by 67 percent and the average daily intakes
by 3-fold. The higher plasma concentrations were reached within
six to nine months of supplementation and were maintained throughout
the trial, although a small decline was seen over the course of
The results of the study showed that total cancer incidence was
significantly lower in the selenium group than in the placebo group
(77 cases versus 119), as was the incidence of some site-specific
cancers: the selenium group had fewer prostate cancers (13 versus
35), fewer colorectal cancers (8 versus 19), and fewer lung cancers
(17 versus 31). These differences were statistically significant.
The number of cases at other sites were insufficient for a valid
The results also showed that over-all mortality was 17 percent
less in the selenium versus the control group (108 versus 129) with
this difference largely due to a 50 percent reduction in cancer
deaths (29 versus 57). Lung cancer deaths were lower in the selenium-treatment
group than in the placebo (12 versus 26). The number of deaths for
other cancers were insufficient for meaningful statistical analysis.
There was no significant difference between the two treatment groups
for other causes of death.
Peter Greenwald, M.D., director of the National Cancer Institutes
Division of Cancer Prevention and Control commented, "These results
are interesting for several reasons. First, there was no detectable
increase in adverse effects from the supplementation which is very
important to know for future trials. Secondly, beneficial effects
were seen for three major cancers."
"Having said all that," he added, "we need to be cautious." Greenwald
noted that the study population was relatively small and consisted
of people who live in low-selenium regions and are at high risk
for non-melanoma skin cancer. The lower cancer rates were found
for cancers that were secondary, not primary study endpoints. The
work, he believes, needs to be confirmed in a larger population
more representative of the U.S.
Selenium soil levels were first associated inversely with cancer
mortality in the late 1960s. Similar results were found in prospective
studies which measured selenium status by several methods; soil,
blood, nails, hair. Some studies have also found inverse associations
with the incidence of cancers of the lung, colon, bladder, rectum,
breast, pancreas, and ovary. However, several studies have shown
no association between selenium status and cancer and a few have
shown a direct association -- cancer risk increased with selenium
In animals, selenium administration has been shown to have antitumor
activity, but at levels several times greater than the nutritional
needs. Likewise, in tissue culture experiments, supplementation
of cultured tumor cells with selenium at much higher doses than
the cells normally require, has been shown to inhibit tumor growth
and stimulate apoptosis, programmed cell death.
Three human intervention studies with selenium have had various
outcomes. The low soil selenium content in Finland led the Finnish
government to begin adding selenium to fertilizers in l984 with
an eye towards reducing cancer risk and cardiovascular disease.
No significant effects on cancer incidence have been seen to date
in the Finnish population of four million.
Two additional human intervention trials took place in Linxian,
China from l985-1991. In one trial, a daily supplement containing
50 ug selenium plus three other minerals and vitamins, had no effect
on the high incidence of esophageal cancer or total cancer incidence
or mortality. The second and largest trial showed a significant
reduction in stomach cancer incidence (16 percent) and stomach cancer
mortality (21 percent) using a daily mixture of antioxidants --
one component of which was selenium.
The current study is the first double-blinded cancer prevention
trial to test whether a nutritional supplement of selenium alone
can reduce cancer risk. Participating dermatology clinics were located
in Augusta, Ga; Macon, Ga; Columbia, S.C.; Miami, Fla; Wilson, N.C.;
Greenville, N.C.; and Newington, Conn.
Greenwald commented on the possibility of future prevention trials. "This
study highlights the value of clinical trials in cancer prevention.
The interesting observation of a possible benefit of selenium needs
to be assessed in a larger, more definitive trial."
* The study is titled: "Effects of Selenium Supplementation for
Cancer Prevention in Patients with Carcinoma of the Skin." The authors
are Larry C. Clark, Gerald. F Combs Jr., Bruce W. Turnbull, Elizabeth
H. Slate, Daniel K. Chalker, James Chow, Loretta S. Davis, Renee
A. Glover, Gloria F. Graharn, Earl G. Gross, Arnon Krongrad, Jack
Lesher, H. Kim Park, Beverly B. Sanders Jr., Cameron L. Smith, J.
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