Unlike some animal, ecologic, case-control, and prospective studies
that have associated higher selenium levels with reduced cancer
risk, a large cohort study recently reported in the Journal
of the National Cancer Institute found that selenium intake
(as reflected by toenail selenium levels) within the range typically
consumed by most women in the United States was not associated
with a reduced risk of several common cancers.
Miriam Garland, SCD, Harvard School of Public Health, led the
research team that analyzed toenail clippings (which may reflect
dietary selenium intake over the previous year or longer) obtained
from 62,641 women with no cancer history. All of the women were
participants in the Nurses' Health Study, and were aged 30 to
55 years at the study's inception in 1976.
The toenail clippings were requested from the cancer-free women
in 1982, and during 41 months of follow-up, 503 cases of cancer
other than breast cancer or nonmelanoma skin cancer were diagnosed.
For each cancer patient, a control subject was chosen from among
the women who remained free of diagnosed cancer, matched by age
and by date of nail return. In addition, toenail selenium data
from a previous study of 434 breast cancer patients and their
controls were included in some of the analyses.
For cancers at all sites combined (excluding breast cancer), case
and control subjects had similar mean toenail selenium levels,
and a nonsignificant positive association between selenium levels
and cancer risk (age- and smoking-adjusted) was found. Potentially
confounding factors were considered (eg, state of residence, weight
relative to height, aspirin use, intake of various dietary constituents,
reproductive variables, and variables related to hormone use and
melanoma risk), but none materially altered the results. In a
combined analysis, including the breast cancer study data, the
results were more weakly positive.
In the analyses by cancer site, toenail selenium level was not
associated with reduced cancer risk at any major site, including
uterine cancer, colorectal cancer, melanoma, ovarian cancer, or
lung cancer (after adjusting for smoking). In fact, nonsignificant
positive associations were observed for colorectal cancer, melanoma,
and for lung cancer. Relevant potential confounding factors were
considered for each of the cancer sites; inclusion of these factors
did not substantially alter the results, except that results for
colorectal and uterine cancer became more strongly positive, though
the trends were not statistically significant.
The authors conclude that the data provide evidence against the
hypothesis of an overall protective effect of selenium within
the range of intakes among women in the U.S. but acknowledge that
the implications of the observed positive associations are unclear.
In addition, they note that knowledge of selenium metabolism is
incomplete, and suggest further research in this area that may
help elucidate the biological basis for any relationship between
selenium and cancer risk.
In an accompanying editorial, Larry C. Clark, MPH, PhD, and David
S. Alberts, MD, Arizona Cancer Center, suggest that despite the
magnitude of this cohort study, interpretation of the results
is complicated by possible selenium status differences in population
subgroups with particular cancer risks from age, exposure or nutrient
status, changes in participants' toenail selenium levels over
time, and other factors. They believe, in light of conflicting
results from epidemiologic studies, that the findings from this
study should not be the sole basis upon which individual or public
health decisions are made. They emphasize the importance of prospective
clinical trials of selenium to address the issue of cancer prevention