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

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Vitamin D and Breast Cancer: Mechanistic Update

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

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

• 25 Meta-analyses of Vitamin D and Breast Cancer
    example: 2X reduction of deaths from Breast Cancer if have enough Vitamin D.
• Appears that having lots of Vitamin D will reduce by 3 X the chance of Breast Cancer
     wonder just how much more proof is needed
• Breast Cancer 4X more likely if have poor genes
•     Cancer - Breast category listing has 259 items along with related searches
• Breast Cancer treatment – Vitamin D was the most-popular supplement – Jan 2023
• Breast Cancer again associated with low vitamin D – 15th meta-analysis Sept 2020
• Vitamin D reduced Breast Cancer mortality in 9 out of 9 studies, yet still no consensus – April 2019
• Vitamin D both prevents and treats Breast Cancer – 2019

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Breast Cancer and Vitamin D Receptor studies

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Breast Cancer and Vitamin Gene studies

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Studies: Breast Cancer and CYP27B1

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Category listing: Genetics

343 articles in the Genetics category

see also

• Vitamin D Receptor has 530 items
• Vitamin D Binding Protein = GC has 178 items
• CYP27B1 has 63 items
• CYP24A1 in title of 34+ items
• CYP2R1 25+ items
• Calcidiol has 48 items
• Calcitriol has 62 items
• Topical Vitamin D
• Nanoemulsion Vitamin D may be a substantially better form
• 1289 genes changed with higher doses of Vitamin D - RCT Dec 2019
• CYP3A4 (7 as of Dec 2022)
• Getting Vitamin D into your body
• 

Vitamin D blood test misses a lot

• 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
      especially if it is one of 51+ diseases related to Vitamin D Receptor
  2) Slightly increasing Vitamin D shows benefits (even if conventional Vitamin D test shows an increase)
  3) DNA and VDR tests - 100 to 200 dollars $100 to $250
  4) PTH bottoms out ( shows that parathyroid cells are getting Vitamin d)
     Genes are good, have enough Magnesium, etc.
  5) Back Pain
     probably want at least 2 clues before taking adding vitamin D, Omega-3, Magnesium, Resveratrol, etc
  • The founder of VitaminDWiki took action with clues #3&5

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Category listing - CYP27B1

The CYP27B1 gene activates Vitamin D in the Kidney,    Skin,    Lungs,    Brain,   Eyes   Breasts   etc.
Poor CYP27B1 is assocated with COVID, Miscarriage,   Lupus,   Alz, Parkinson, MSA,   Rickets

CYtochrome P450 family 27 subfamily B member 1    = 25-Hydroxyvitamin D3 1-alpha-hydroxylase

• 63 items in CYP27B1 category
• 343 articles in the Genetics
• 530 articles in Vitamin D Receptor
• 178 articles in Vitamin D Binding Protein
• CYP27B1 and other genes are less activated in seniors
• CYP27B causes many health problems – March 2020
• Every Parkinson’s brain had a poor CYP27B1 gene

What can be done if have a poor CYP27B1

• Larger doses of Vitamin D
• More Bio-available: Gut-friendly form, Topical form, taken with fatty meal, taken with evening meal
• Additional sources: UV
• Increase Vitamin D metabolism: additional Magnesium, Omega-3
  • All cytochrome P450 enzymes require Mg++ as a cofactor
• Increase the amount of Vitamin D in the blood that gets to cells: increase activation of VDR
  • See: Reasons for low response to vitamin D

Vitamin D blood test misses CYP27B1 and other genes

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Cancers might alter the CYP24A1 gene

CYP24A1 gene and Vitamin D - many studies

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Vitamin D Receptor category with CANCER in the title (76 as of Feb 2022)

This list is automatically updated