Epidemiological studies suggest that vitamin D deficiency may be associated with higher incidence of breast cancer (1–4). However the dose-response relationship is unclear. To estimate the amount of vitamin D required for nutritional fortification to reduce incidence of breast cancer, we performed a meta-analysis of the dose-response gradient between serum 25-hydroxyvitamin D (25(OH)D) and risk of breast cancer. Studies were identified that included 1,760 individuals. Dose-response curves were plotted for pooled data. The pooled quintiles of 25(OH)D were 0-11, 12–25, 26–31, 32–42 and > 42 ng/ml. Odds ratios for breast cancer from lowest to highest quintile, were 1.00, 0.90, 0.70, 0.70, and 0.50 (p trend < 0.0002). According to multiple regression, a 25(OH)D level of > 52 ng/ml was associated with 50% lower risk of breast cancer compared to women with < 12 ng/ml. This is higher than the concentration of 25(OH)D that would be associated with a 50% reduction in colorectal cancer (33 ng/ml) (5). Intake of > 2,700 IU/day of vitamin D3 would be required to maintain this level in a 70-kg individual (6–7). This is higher than the National Academy of Sciences current No Adverse Effect Level (NOAEL) of 2,400 IU/day, and upper limit of 2,000 IU/day, although lower than the NAS Lowest Observed Adverse Effect Level of 3,800 IU/day. Consideration should be given to revising the upper limit and the adequate intake (200-800 IU/day), and to greater fortification of food with vitamin D3 than is done at present. The US median intake of 320 IU/day is only about one tenth of the amount required for reduction of breast cancer incidence by 50% compared to women with < 12 ng/ml, based on observational studies. Greater vitamin D3 intake is needed since many individuals have inadequate UVB exposure due to indoor occupations and sunscreens. References: 1. Gorham ED et al. Can J Publ Health 1989;80:96–100. 2. Garland FC, et al. Prev Med 1990;19:614–22. 3. Gorham ED et al. Int J Epidemiol 1990;19:820–4 4. Grant WB. Cancer 2002;94:272–81. 5. Gorham ED et al. J Steroid Biochem Molec Biol 2005 (in press) 6. Heaney RP et al. Am J Clin Nutr 2003;77:204–10. 7. Zitterman A. Am J Clin Nutr 2003;78:456–7.

[Proc Amer Assoc Cancer Res, Volume 47, 2006]