Plasma 25-Hydroxyvitamin D and Risk of Breast Cancer in Women Followed over 20 Years

Abstract

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. Results Plasma 25(OH)D levels were not associated with breast cancer risk overall (top (≥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 (≥30ng/mL vs. <30ng/mL RR (95% CI): VDR≥median=0.67 (0.48–0.93); VDR<median=0.98 (0.72–1.35), p-heterogeneity=0.12), and significantly stronger for summer measures (p-heterogeneity=0.01). Associations were not significantly different by RXR expression. No overall association was observed between plasma 25(OH)D and breast cancer risk. However, our results suggest women with high, compared with low, plasma 25(OH)D levels in the summer have a reduced breast cancer risk, and plasma 25(OH)D may be inversely associated with risk of tumors expressing high levels of VDR.

Dietary Supplements Commonly Used by Cancer Survivors: Are There Any Benefits?

“…In a recent study by Eliassen et al, no overall association was found between plasma 25(OH)D levels and risk for breast cancer, although a reduced risk was found for women having higher levels when compared with the those in the lowest quintile in the summer (RR, 0.66; 95% CI, 0.46–0.94; P trend = .01) 57 . More recently, McDonnell et al reported that in women with 25(OH)D levels ≥40 ng/mL, a 67% lower risk of breast cancer was found vs women having serum levels <20 ng/mL (HR, 0.33; 95% CI, 0.12–0.90) 58 .…”

“…Worldwide, plants have been used for healing since ancient times 57 . Only recently has the interest in using botanicals for medicine risen in the United States, while in Asia, South America, and Africa, the use of local plants is a primary component of medical treatment.…”

Histone deacetylase activity and vitamin D‐dependent gene expressions in relation to sulforaphane in human breast cancer cells

“…Sulforaphane was found to inhibit proliferation, angiogenesis, and metastasis as well as induce cell cycle arrest and apoptosis in breast cancer cells. In addition, sulforaphane has a marked effect on cell cycle checkpoint controls, cell survival, and/or apoptosis in various other cancer cell lines, though the molecular mechanisms remain poorly understood (Eliassen et al, 2016;Park et al, 2015;Sofi et al, 2018).…”

Function of the vitamin D endocrine system in mammary gland and breast cancer

“…More importantly, confirmation of a link between vitamin D status and breast cancer would raise the possibility that breast cancer development or survival could be modified by strategies to increase serum 25D such as food fortification, use of dietary supplements or prudent increases in sun exposure. While a substantial amount of epidemiological and clinical data support such associations, the cumulative data is inconsistent (4; 9–12). In many epidemiological studies, the impact of vitamin D status appeared to be limited to sub-groups in a cohort with specific attributes, such as pre- or post- menopausal status, presence of obesity, specific tumor subtype, race/ethnicity or genetic polymorphisms.…”