Vitamin C (ascorbic acid) is also an antioxidant and can block the formation of carcinogenic nitrosamines. Few animal studies have assessed the effect of vitamin C on mammary cancer; in a study in rats, ascorbic acid had no effect on the growth of either transplanted or dimethylbenzanthracene-induced mammary tumors.
In the largest case control study reported, no effect for vitamin C was observed; however, in a subsequent study by the same group, a significant protective effect was present (relative risk of 0.6 for highest versus lowest quartile). In a meta-analysis of nine other case control studies with data on vitamin C, a significant inverse association (relative risk of 0.7 for each 300 mg per day increase in vitamin C) was observed.
In prospective studies, however, no significant association between intake of vitamin C and breast cancer was observed. In the 14-year follow-up of the Nurses’ Health Study, no evidence of any reduction in risk was seen with long-term use of vitamin C supplements. Thus, the existing data on intake of vitamin C and breast cancer risk are somewhat inconsistent. However, the available prospective data do not support benefits of high vitamin C intake for reducing breast cancer risk.
Selenium is an important component of the antioxidant enzyme glutathione peroxidase, inhibits cell proliferation, and, in animal studies, has been shown to protect against a variety of cancers, although usually at high levels of intake. In the United States, ecological studies have shown strong inverse associations between county-specific and national measures of selenium exposure and breast cancer rates.
Selenium intake cannot be measured accurately by means of dietary assessment in geographically dispersed populations, because the selenium content of individual foods varies greatly depending on the geographic area in which the foods were grown. Selenium levels in tissues such as blood and toenails do reflect selenium intake, however, and thus provide an informative measure of diet.
Several studies using these biomarkers of selenium intake have been performed. In one relatively small study, a nonsignificant positive association was observed between erythrocyte selenium level and breast cancer. In the largest prospective study, Hunter et al. observed no association between selenium levels in toenail and risk of breast cancer during 4 years of follow-up.
Of the other prospective studies, only the study of Knekt et al. from Finland showed any evidence of an increased risk among women in the lowest category of selenium level. As women in Finland at that time had extremely low selenium intakes, this observation is consistent with the possibility that a threshold exists below which low selenium intake does increase breast cancer risk. In a small randomized trial, breast cancer was the only malignancy that occurred more frequently among those receiving selenium supplements. Taken together, these data suggest that increases in selenium intake are unlikely to reduce risk of breast cancer for most women in countries with existing moderate or high levels of selenium intake.
Walter C. Willett, Beverly Rockhill, Susan E. Hankinson, David J. Hunter and Graham A. Colditz
W. C. Willett: Harvard Medical School, Boston, Massachusetts; Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts
B. Rockhill: Harvard Medical School, Brigham and Women’s Hospital, Boston, Massachusetts
S. E. Hankinson: Departments of Medicine and Epidemiology, Harvard Medical School and Harvard School of Public Health, Boston Massachusetts
D. J. Hunter: Departments of Epidemiology and Nutrition, Harvard School of Public Health, Boston, Massachussetts
G. A. Colditz: Department of Medicine, Harvard Medical School, Boston, Massachussetts