Vitamin D and Breast Cancer. Studies on Incidence and Survival

Abstract: AbstractPrevious research has suggested beneficial effects of vitamin D on both breast cancer risk and prognosis. The overall aim of this research project was to investigate associations between vitamin D and breast cancer. The population-based prospective cohort, the Malmö Diet and Cancer Study, recruited 17,034 women in the first half of the 1990s. Studies in in the current thesis are based on blood samples collected at baseline, analyzed for levels of vitamin D, parathyroid hormone (PTH), calcium and later also used for genetic sequencing. Breast tumors that developed in women within the cohort were included in a tissue microarray and analyzed for expression of the vitamin D receptor (VDR). Specific aims were to investigate: I. Serum levels of vitamin D, PTH and calcium in relation to breast cancer survival, i.e. mortality among women diagnosed with breast cancer. II. Vitamin D-related single nucleotide polymorphisms (SNPs) and breast cancer risk.III. Expression of VDR in association with breast cancer mortality.IV. Levels of vitamin D in relation to expression of VDR in subsequent breast tumors. Results and conclusions:I. Compared to intermediate levels of vitamin D, low levels and high levels were associated with a poor survival, i.e. high risk of death related to breast cancer. No association was found between PTH and breast cancer mortality. Relatively high serum calcium levels were associated with relatively low breast cancer mortality.II. SNPs associated with levels of vitamin D did not affect breast cancer risk. One SNP, related to the vitamin D binding protein, was associated with breast cancer risk.III. VDR expression was associated with a favorable breast cancer prognosis.IV. There were indications that vitamin D levels were associated with VDR expression in a subsequent breast tumor.The association between low vitamin D levels and high breast cancer mortality may be mediated through development of a VDR-negative tumor. There was no evidence to suggest an additional beneficiary effect of vitamin D levels higher than intermediate levels.

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