Current issues of ACP Journal Club are published in Annals of Internal Medicine


Low selenium was not a risk factor for breast cancer

ACP J Club. 1991 Jan-Feb;114:28. doi:10.7326/ACPJC-1991-114-1-028

Source Citation

Hunter DJ, Morris JS, Stampfer MJ, et al. A prospective study of selenium status and breast cancer risk. JAMA. 1990;264:1128-31.



To determine whether low selenium dietary intake, as reflected in selenium content of toenail clippings, is a risk factor for the development of breast cancer in women.


Double-blind, case-control study of matched pairs of women from a cohort followed from 1976 to 1986.


The Nurses Health Study, centered in Boston, Massachusetts, including women from 11 states.


62 641 registered nurses from a volunteer cohort, age 30 to 55 years in 1976, had no history of cancer and sent in a set of toenail clippings in 1982. Their mean response rate to questionnaires in 1984 and 1986 was 95.9%. 435 women who reported a diagnosis of breast cancer were paired with randomly selected controls matched by year of birth and date of return of nail clippings.

Assessment of risk factors

Selenium content of toenail clippings was analyzed (without case identification) by measuring isomeric transition of radioactive selenium. Information on reproductive history, family history, smoking, and other risk factors was collected from the questionnaires.

Main outcome measures

Patients or next of kin reported incident breast cancer and deaths. Hospital records and pathology reports were examined for confirmation of the diagnosis for 416 of the 435 cases.

Main results

The distribution of toenail selenium between cases and controls was not statistically significant. Means differed by 0.2% (cases, 0.823 µg/g, controls, 0.821 µg/g, P = 0.9). When women in the highest quintile of toenail selenium content were compared with those in the lowest quintile, the relative risk for breast cancer was 1.10 (95% CI 0.70 to 1.72) after adjusting for other breast cancer risk factors. There was no linear trend across quintiles. Selenium content was significantly related to 2 potential risk factors for breast cancer: Current smokers had lower mean levels (0.778 µg/g) than those who had never smoked (0.834 µg/g, P = 0.01) and women who had reached menarche before 13 years had lower mean levels (0.805 µg/g) than those who reached menarche at 13 years or more (0.837 µg/g, P = 0.05).


A low level of selenium in toenail clippings of adult women was not a risk factor for development of breast cancer 1 to 53 months later.

Source of funding: National Institutes of Health.

Address for article reprint: Dr. D.J. Hunter, Nurses Health Study, Channing Laboratory, 180 Longwood Avenue, Boston, MA 02115-5899, USA.


Selenium inhibits mammary carcinogenesis in rodents, and some epidemiologic data suggest that selenium may protect against breast cancer in humans. In this study, selenium was measured in toenail clippings from 62 641 nurses who were members of a large cohort in which risk factors for cancer and heart disease were being assessed. No relation was found in a subsample of the cohort between the selenium content of toenails—a valid measure of selenium intake over time—and the development of breast cancer. Although selenium intake was not associated with breast cancer in this study, a possible role for selenium in cancer prevention cannot be excluded at levels of intake outside the range observed here, at earlier times in life, or on the incidence of cancers other than breast cancer. These data, however, provide no justification for recommending selenium supplements to reduce risk for breast cancer in adults.

Norman Boyd, MD
Ontario Cancer InstituteToronto, Ontario, Canada