Associations between polymorphisms in the vitamin D receptor and breast cancer risk.
Biological and epidemiologic data suggest that vitamin D levels may influence breast cancer development. The vitamin D receptor (VDR) is a crucial mediator for the cellular effects of vitamin D and additionally interacts with other cell-signaling pathways that influence cancer development. Because functional data exist on FOK1 and previous studies have suggested a relation between BSM1 and breast cancer risk, we evaluated the associations of the FOK1 and BSM1 VDR polymorphisms and breast cancer risk. In a case-control study nested within the Nurses' Health Study, we genotyped 1,234 incident cases (diagnosed between return of a blood sample in 1989-1990 and June 1, 2000) and 1,676 controls for FOK1, and 1,180 cases and 1,547 controls for BSM1. We observed a significantly increased risk of breast cancer among carriers of the ff genotype of FOK1 (multivariate odds ratio, 1.34; 95% confidence intervals, 1.06-1.69) compared with those with FF. We did not observe an association between polymorphisms in BSM1 and breast cancer risk (multivariate odds ratio, 0.93; 95% confidence intervals, 0.72-1.20) for BB versus bb). The FOK1 association did not vary significantly by menopausal status, estrogen, and progesterone receptor status of the tumors, or plasma levels of 25 hydroxyvitamin D or 1,25 dihydroxyvitamin D. Our results suggest that the VDR may be a mediator of breast cancer risk and could represent a target for cancer prevention efforts.
Chen
Wendy Y
WY
Channing Laboratory, Harvard Medical School, 181 Longwood Avenue, Boston, MA 02115, USA. wendy.chen@channing.hardvard.edu
Bertone-Johnson
Elizabeth R
ER
Hunter
David J
DJ
Willett
Walter C
WC
Hankinson
Susan E
SE
D000328:Adult; D014408:Biomarkers, Tumor / Q000097:blood; D001943:Breast Neoplasms / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D011110:Polymorphism, Genetic; D018167:Receptors, Calcitriol / Q000235:genetics*; D014807:Vitamin D / Q000097:blood
D014408:Biomarkers, Tumor; D018167:Receptors, Calcitriol; D014807:Vitamin D