Multiple lines of evidence suggest that vitamin D intake may improve survival after a breast cancer diagnosis. Several human and animal studies have linked either dietary intake of vitamin D, vitamin D blood levels, or sun exposure with reduced risk of breast cancer incidence or breast cancer mortality. 1,25-Dihydroxyvitamin D (1,25(OH)2D), the biologically active form of vitamin D, can induce differentiation and apoptosis of transformed mammary cells. Vitamin D analogs are being explored as cancer therapeutic agents. In 1999, we reported a marginally significant reduced risk of death (378 deaths) among nearly 2000 participants with breast cancer, in the Nurses' Health Study (NHS), associated with higher vitamin D intake from food; to our knowledge, no other observational study has reported on vitamin D intake and survival after breast cancer. We propose to examine vitamin D intake and survival after a breast cancer diagnosis, in the NHS; we will expand on our previous report by utilizing 10 more years of follow-up, 5,000 more breast cancer survivors, and over 2000 deaths from breast cancer. In addition, we will also use a model for vitamin D status, developed in a subset of NHS participants with plasma 25-hydroxy vitamin D (25(OH)D) measurements, based on body mass index, region of inhabitance and physical activity as indicators for sunlight exposure, race as an indicator for skin pigmentation, and diet. We hypothesize that higher vitamin D intake and predicted vitamin D status after a breast cancer diagnosis are associated with a reduced risk of death from breast cancer. The vitamin D receptor (VDR) is a critical mediator of the cellular effects of vitamin D. A polymorphism in VDR (FOK1) has been shown to influence breast cancer risk. We hypothesize that women homozygous for this polymorphism will have an increased risk of death from breast cancer.
