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Breast Cancer, Vitamin D, and genes – Welsh Nov 2021


Vitamin D and Breast Cancer: Mechanistic Update

JMBR doi: 10.1002/jbm4.10582
JoEllen Welsh, PhD

ABSTRACT

The presence of the vitamin D receptor (VDR) in mammary gland and breast cancer has long been recognized, and multiple pre-clinical studies have demonstrated that its ligand 1,25- dihydroxyvitamin D (1,25D) modulates normal mammary gland development and inhibits growth of breast tumors in animal models. Vitamin D deficiency is common in breast cancer patients and some evidence suggests that low vitamin D status enhances the risk for disease development or progression. Although many 1,25D responsive targets in normal mammary cells and in breast cancers have been identified, validation of specific targets that regulate cell cycle, apoptosis, autophagy and differentiation, particularly in vivo, has been challenging. Model systems of carcinogenesis have provided evidence that both VDR expression and 1,25D actions change with transformation, but clinical data regarding vitamin D responsiveness of established tumors is limited and inconclusive. Because breast cancer is heterogeneous, the relevant VDR targets and potential sensitivity to vitamin D repletion or supplementation will likely differ between patient populations. Detailed analysis of VDR actions in specific molecular subtypes of the disease will be necessary to clarify the conflicting data. Genomic, proteomic and metabolomic analyses of in vitro and in vivo model systems is also warranted to comprehensively understand the network of vitamin D regulated pathways in the context of breast cancer heterogeneity. This review provides an update on recent studies spanning the spectrum of mechanistic (cell/molecular), pre-clinical (animal models) and translational work on the role of vitamin D in breast cancer.

Summary.

Breast cancers are highly heterogeneous, yet many express VDR suggesting that vitamin D status may be clinically relevant for women living with this disease. Mechanistic studies have demonstrated that vitamin D signaling opposes multiple proliferative pathways in both normal breast tissue and in breast cancers, including those driven by reproductive hormones. Recent studies in model systems have highlighted inhibitory effects of vitamin D signaling on EMT and breast cancer stem cells which would be predicted to reduce their capacity to drive metastasis, drug resistance and poor survival. These effects include inhibition of CD44 signaling via disruption of HAS2 production of its ligand HA. In addition, vitamin D has the potential to modulate various non-cancerous cell types in the tumor microenvironment to promote tumor immunity and inhibit tumor angiogenesis. Translation of these findings into prevention or treatment of human breast cancer will require attention to several research gaps including identification of common and relevant VDR targets in distinct breast cancer subtypes, clarification of the mechanisms and importance of accumulation and turnover of vitamin D metabolites in tumors and discovery of regulatory mechanisms that enhance vitamin D signaling in the TME.
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VitaminDWiki

Overview Breast Cancer and Vitamin D

Overview Breast Cancer and Vitamin D


Breast Cancer and Vitamin D Receptor studies


Breast Cancer and Vitamin Gene studies


Studies: Breast Cancer and CYP27B1


Category listing: Genetics

283 articles in the Genetics category

see also

Vitamin D blood test misses a lot
Blood Test Misses a lot (VDW 3439)

  • Snapshot of the literature by VitaminDWiki as of early 2019
  • Vitamin D from coming from tissues (vs blood) was speculated to be 50% in 2014, and by 2017 was speculated to be 90%
  • Note: Good blood test results (> 40 ng) does not mean that a good amount of Vitamin D actually gets to cells
  • A Vitamin D test in cells rather than blood was feasible (2017 personal communication)
  •    Commercially available 2019
    • However test results would vary in each tissue due to multiple genes
  • Good clues that Vitamin D is being restricted from getting to the cells
    1) A vitamin D-related health problem runs in the family
    2) Slightly increasing Vitamin D show benefits (even if conventional Vitamin D test shows an increase)
    3) Vitamin D Receptor test (<$30) scores are difficult to understand in 2016
    • easier to understand the VDR 23andMe test results analyzed by FoundMyFitness in 2018

    4) Back Pain

Category listing - CYP27B1

The CYP27B1 gene activates Vitamin D in the Kidney,    Skin,    Lungs,    Brain,   Eyes   Breasts   etc.
CYtochrome P450 family 27 subfamily B member 1    = 25-Hydroxyvitamin D3 1-alpha-hydroxylase

Vitamin D blood test misses CYP27B1 and other genes
Blood Test Misses a lot (VDW 3439)


Cancers might alter the CYP24A1 gene

CYP24A1 enzyme and Vitamin D


Created by admin. Last Modification: Wednesday November 17, 2021 11:45:50 GMT-0000 by admin. (Version 6)

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