Vitamin D status and breast cancer risk.
BACKGROUND
Local synthesis of 1alpha,25(OH)D3 in breast tissue may contribute to maintenance of normal cell function and could be impaired with low circulating levels of the precursor 25hydroxyvitamin D. The aims of this study were to: i) assess the association between breast cancer risk and plasma 25OHD3 concentration and ii) define the significance of expression of the 25OHD activating enzyme CYP27b1 in non-malignant and malignant models of breast epithelial cells.


METHODS
Breast cancer patients and control women were recruited and their 25OHD levels measured by enzyme-linked immunosorbent assay (ELISA). MRNA expression of CYP271b and the 1,25(OH)2D3 inactivating enzyme CYP24 were measured in breast cancer cell lines by RT-PCR and correlated with immunoblotting approaches to the translated proteins.


RESULTS
For women with 25OHD < 50 nM the odds ratio for breast cancer compared with women with 25OHD > 50 nM was 3.54 (CI 1.89-6.61, p < 0.001). CYP271b and CYP24 were detected in non-malignant and malignant cell models. Protein levels of 24OHase but not 1alphaOHase were decreased at confluence in the cell lines.


CONCLUSIONS
Impaired local generation of 1,25OHD3 may contribute to the development of breast cancer.
Colston
Kay W
KW
Department of Clinical Biochemistry, St. George's Hospital Medical School, London SW15, UK.
Lowe
Lorraine C
LC
Mansi
Janine L
JL
Campbell
Moray J
MJ
D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D001943:Breast Neoplasms / Q000097:blood* / Q000188:drug therapy / Q000235:genetics; D002112:Calcifediol / Q000097:blood*; D002117:Calcitriol / Q000494:pharmacology; D016022:Case-Control Studies; D048708:Cell Growth Processes / Q000187:drug effects; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D006887:Hydroxycholecalciferols / Q000494:pharmacology; D011110:Polymorphism, Genetic; D018167:Receptors, Calcitriol / Q000235:genetics; D012307:Risk Factors; D013250:Steroid Hydroxylases / Q000378:metabolism; D065668:Vitamin D3 24-Hydroxylase
D006887:Hydroxycholecalciferols; D018167:Receptors, Calcitriol; C013721:1,24,25-trihydroxyvitamin D3; D013250:Steroid Hydroxylases; D065668:Vitamin D3 24-Hydroxylase; D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase; D002117:Calcitriol; D002112:Calcifediol