Study Shows No Reduced Cancer Risk in Women From Average Selenium Intake

Unlike some animal, ecologic, case-control, and prospective studiesthat have associated higher selenium levels with reduced cancerrisk, a large cohort study recently reported in the Journalof the National Cancer Institute found that selenium intake(as reflected by toenail selenium levels) within the range typicallyconsumed by most women in the United States was not associatedwith a reduced risk of several common cancers.

Miriam Garland, SCD, Harvard School of Public Health, led theresearch team that analyzed toenail clippings (which may reflectdietary selenium intake over the previous year or longer) obtainedfrom 62,641 women with no cancer history. All of the women wereparticipants in the Nurses' Health Study, and were aged 30 to55 years at the study's inception in 1976.

The toenail clippings were requested from the cancer-free womenin 1982, and during 41 months of follow-up, 503 cases of cancerother than breast cancer or nonmelanoma skin cancer were diagnosed.For each cancer patient, a control subject was chosen from amongthe women who remained free of diagnosed cancer, matched by ageand by date of nail return. In addition, toenail selenium datafrom a previous study of 434 breast cancer patients and theircontrols were included in some of the analyses.

For cancers at all sites combined (excluding breast cancer), caseand control subjects had similar mean toenail selenium levels,and a nonsignificant positive association between selenium levelsand cancer risk (age- and smoking-adjusted) was found. Potentiallyconfounding factors were considered (eg, state of residence, weightrelative to height, aspirin use, intake of various dietary constituents,reproductive variables, and variables related to hormone use andmelanoma risk), but none materially altered the results. In acombined analysis, including the breast cancer study data, theresults were more weakly positive.

In the analyses by cancer site, toenail selenium level was notassociated with reduced cancer risk at any major site, includinguterine cancer, colorectal cancer, melanoma, ovarian cancer, orlung cancer (after adjusting for smoking). In fact, nonsignificantpositive associations were observed for colorectal cancer, melanoma,and for lung cancer. Relevant potential confounding factors wereconsidered for each of the cancer sites; inclusion of these factorsdid not substantially alter the results, except that results forcolorectal and uterine cancer became more strongly positive, thoughthe trends were not statistically significant.

The authors conclude that the data provide evidence against thehypothesis of an overall protective effect of selenium withinthe range of intakes among women in the U.S. but acknowledge thatthe implications of the observed positive associations are unclear.In addition, they note that knowledge of selenium metabolism isincomplete, and suggest further research in this area that mayhelp elucidate the biological basis for any relationship betweenselenium and cancer risk.

In an accompanying editorial, Larry C. Clark, MPH, PhD, and DavidS. Alberts, MD, Arizona Cancer Center, suggest that despite themagnitude of this cohort study, interpretation of the resultsis complicated by possible selenium status differences in populationsubgroups with particular cancer risks from age, exposure or nutrientstatus, changes in participants' toenail selenium levels overtime, and other factors. They believe, in light of conflictingresults from epidemiologic studies, that the findings from thisstudy should not be the sole basis upon which individual or publichealth decisions are made. They emphasize the importance of prospectiveclinical trials of selenium to address the issue of cancer preventiondirectly.