Experimental evidence supports a protective role of 25-hydroxyvitamin D (25(OH)D) in breast carcinogenesis, but epidemiologic evidence is inconsistent. Whether plasma 25(OH)D interacts with breast tumor expression of vitamin D receptor (VDR) and retinoid X receptor-alpha (RXR) has not been investigated. We conducted a nested case-control study in the Nurses' Health Study, with 1,506 invasive breast cancer cases diagnosed after blood donation in 1989-90, 417 of whom donated a second sample in 2000-02. VDR and RXR expression were assessed by immunohistochemical staining of tumor microarrays (n=669 cases). Multivariate relative risks (RRs) and 95% confidence intervals (CIs) were calculated using conditional logistic regression.

Plasma 25(OH)D levels were not associated with breast cancer risk overall (top ({greater than or equal to}32.7ng/mL) vs. bottom (<17.2ng/mL) quintile RR=0.87, 95% CI (0.67-1.13), p-trend=0.21). 25(OH)D measured in summer (May-October) was significantly inversely associated with risk (top vs. bottom quintile RR=0.66, 95% CI (0.46-0.94), p-trend=0.01); winter levels (November-April) were not (RR=1.10, 95% CI (0.75-1.60), p-trend=0.64; p-interaction=0.03). 25(OH)D levels were inversely associated with risk of tumors with high expression of stromal nuclear VDR ({greater than or equal to}30ng/mL vs. <30ng/mL RR (95% CI): VDR{greater than or equal to}median=0.67 (0.48-0.93); VDR

Copyright {copyright, serif}2016, American Association for Cancer Research.

PMID:27530324