By Mehir un Nisa Iqbal and Taseer Ahmed Khan, Submitted: November 4th 2015Reviewed: June 6th 2016Published: April 26th 2017, Home > Books > A Critical Evaluation of Vitamin D - Clinical Overview. This highest incidence of breast cancer in American whites and in most European countries reveal the long‐standing high prevalence of reproductive factors associated with increased risk of breast cancer, including early menarche, late child bearing age, few pregnancies, hormone replacement therapy and increased mammography [3, 4]. The gene is 75 kb long and contains 11 exons [103]. The lower breast cancer incidence rate was found in the regions of high solar UVB radiations such as in Australia, China, France, Nordic countries, Spain and the United States [96]. Vitamin D is most essential secosteroid produced its systemic functions via complex with steroid/thyroid nuclear receptor called vitamin D receptor (VDR). Poly (A) tail is a variable number of tandem repeats (VNTR) or short tandem repeats (STR) containing variable numbers of adenine nucleotide present at the 3’ UTR of VDR. Season, latitude, pigmentation of skin, aging, sunscreen use, obesity, and smoking all affect the production of vitamin D. In case of vitamin D deficiency or VDR gene polymorphisms, vitamin D responses are altered and probably are involved in the risk of breast cancer. Vitamin D Receptor Antagonists for Treating Breast Cancer Vitamin D receptor (VDR) is a nuclear receptor that is activated by calcitriol, the active form of vitamin D. It is best known for regulating dietary calcium uptake necessary for bone growth, but it also affects cell proliferation and differentiation. Calcitriol binds to VDR, which then forms a heterodimer with the retinoid-X receptor. Changes in the redox state could translate into reversible oxidation of cysteines in major proteins that determine cell fate, such as protein kinases, protein tyrosine phosphatases and transcription factors (e.g. 1,25 (OH)2D (bound to DBP) moves from the kidney , or the tissue itself, into the nucleus. Note: Many people have Herpes but are not aware of it. The vitamin D receptor (VDR) is a member of the nuclear receptor/steroid hormone receptor superfamily. Licensee IntechOpen. Within this model, photoperiod at conception and plasma 25(OH)D independently predicted methylation density at the VDR-CpG island. for blacks – meta-analysis Nov 2012, Vitamin D levels are strongly associated with genes: overview of twin studies – Nov 2012, Breast Cancer incidence change by 40 percent with vitamin D receptor genes – Oct 2012, 2X more Thyroid Cancer malignancy if less than 15 ng of vitamin D – June 2012, Hodgkin’s lymphoma and Vitamin D Receptor - June 2012, Hours of sun per week decreased probability of NH lymphoma by 32 percent – April 2012, 10 percent of colon cancer linked to Vitamin D Receptor – meta-analysis April 2012, Alzheimer’s patients are genetically 70 percent more likely to be vitamin D in-efficient – Feb 2012, Vitamin D receptor activation and Chronic Kidney Disease – Oct 2011, Resveratrol gets vitamin D to cells even if poor vitamin D receptor, Brain cancer in 175 countries related to low UVB and low vitamin D – Oct 2010, Genes breast cancer and vitamin D receptor - Sept 2010, 229 Genes related to vitamin D - Aug 2010, Vitamin D Receptor technical details – Jan 2010, Potential for vitamin D receptor agonists in the treatment of cardiovascular disease, Herpes downregulates VDR by 8X for a short time, Natural Ways to Increase Calcitriol and Activate The Vitamin D Receptor Gene, Changes in vitamin D endocrinology during aging in adults. Sunshine Is an Effective Way to Get Vitamin D Vitamin D can be produced from cholesterol … Vitamin D level can be high, but little benefit: due to kidney, genes, low Magnesium etc. The metabolic active form 1,25(OH) 2 D 3 of vitamin D exerts its actions through interaction with the vitamin D receptor, VDR (Bikle 2011). In fact a recent meta‐analysis concluded that high circulating level of vitamin D is weakly related with breast cancer incident; however, strong association was found with better breast cancer survival [89]. The binding of the vitamin D3 to VDR causes conformational changes that permit VDR-RXR heterodimer formation and VDR/ SRC-1 (transcriptional co-activator proteins) interactions. Nemenqani et al. The full metabolic pathway of vitamin D metabolism operates in monocytes: 25 (OH)D is converted to 1,25 (OH)2D and 24,25 (OH)2D is produced in a catabolic pathway that limits excess production of 1,25 (OH)2D. C domain (DNA binding domain or DBD) having two Zn fingers [32] motifs. Vitamin D also reduces the formation of blood vessels around tumours and decreases the ability of tumours to invade [98]. Since breast cancer is a complex disease which may or may not be associated with the decreased vitamin D levels or VDR polymorphisms. Therefore, these SNPs may have the potential to influence the mRNA stability. Again, the kidney converts 25 (OH)D to 1,25 (OH)2D by use of the enzyme 1alpha-hydroxylase. Decrease in SOD levels would cause a shift in the balance between superoxides and hydrogen peroxide (H2O2). Despite these consistent data, the exact mechanism of breast cancer prevention by vitamin D has yet to be discerned. Once calcitriol binds to the VDR, the Vitamin A (retinol) receptor (RXRA and RXRB) is involved in activation of the VDR targets. Contact our London head office or media team here. Two alpha helices are found at the carboxy terminus of each Zn finger (namely helix A and B which constitutes DNA recognition and phosphate binding sites respectively). The mechanism by which vitamin D induced apoptosis has not been fully understood. VDR is a member of nuclear receptor (NR) superfamily and transcription regulating factor also called NR1I1 or nuclear receptor subfamily 1, group I and member 1. It appears that 30% of the population have a poor VDR (40% of the Obese ), A poor VDR increases the risk of 55 health problems click here for details It’s based on principles of collaboration, unobstructed discovery, and, most importantly, scientific progression. Again, UV exposure and plasma 25(OH)D independently predicted methylation density at the VDR-CpG island. LCA travels to the colon, where the VDR binds to LCA or 1,25 D and activates the CYP3A4 and SULT2A genes facilitate disposal from the cell via the ABC efflux transporter [R]. RESULTS: How? The exact reason why a woman develops breast cancer is still unrevealed; though certain risk factors enhance a person’s probability of getting breast cancer. - Sardi May 12, 2020, Genes which reduce blood-level vitamin D increase the risk of Alzheimer’s disease – Dec 2016, Genes which regulate active vitamin D worsen with age – Oct 2016, Hair loss strongly associated with poor vitamin D receptors– Dec 2016, Heart Failure not helped by Vitamin D (several strange things about the trial) – RCT May 2017, Helicobacter pylori infection protection by the body’s increasing Vitamin D receptors – Nov 2013, How should Vitamin D be tested – a changing landscape – June 2016, Hypothesis – Brain plasticity improved by Vitamin D – Feb 2019, Infections and low vitamin D (including deep neck infections), Interactions of Asthma Vitamin D, Pollution and Obesity – July 2019, Live longer if have more than 40 ng of Vitamin D (gene analysis of 10,500 people) – Jan 2019, Live longer with lung cancer if have good vitamin D genes (or perhaps lots of vitamin D) – Dec 2017, Low Vitamin D is a causal factor for Multiple Sclerosis (Mendelian analysis) – Jan 2020, Low Vitamin D is associated with ill health for seniors – review Oct 2019, Lower back pain treated by 600,000 IU of Vitamin D – RCT June 2019, Many Ashkenazi Jewish diseases associated with low vitamin D or poor Vit D genes, Many reasons why vitamin D deficiency has become epidemic, Many US kids have less than 40 ng of Vitamin D – 99 out of 100 blacks, 91 out of 100 whites – Jan 2017, Millennials (1981-1999) are sicker and dying faster than previous generations (Vitamin D can help) – Nov 2019, Miscarriage in first trimester 2.5X more likely if less than 20 ng of vitamin D – July 2015, Miscarriages strongly associated with poor placental, decidua gene which locally activates Vitamin D – Dec 2016, More genes changed with higher doses of Vitamin D (suggest future gene studies) - RCT Dec 2019, Multiple Myeloma (blood cell cancer) treated by vitamin D - many studies, Multiple Sclerosis relapses cut in half by 100,000 IU of Vitamin D every 2 weeks– RCT 2019, Multiple Sclerosis, Alzheimer’s and Parkinson’s need more than 30 ng of Vitamin D – review Nov 2017, My balance significantly improved at age 73 (perhaps Vitamin D, B12, or Omega-3) – Jan 2020, NAFLD is treated by Vitamin D, Omega-3, Curcumin, Silymarinm, etc. 2017 Apr 22. doi: 10.1002/ajhb.23010. Alzheimer’s patients 3X more likely to have a malfunctioning vitamin D receptor gene – 2012, Calcium and vitamin D receptors are important to many health conditions – Jan 2013, Vitamin D Receptor genes bb and BB and Osteoporosis, esp. Immunohistochemistry and in situ hybridization studies indicated strong expression of 1α‐hydroxylase protein and mRNA in the distal convoluted tubule, the cortical and medullary part of the collecting ducts and the papillary epithelia. Hence, Vitamin D and Vitamin A … However, the contribution of non‐genomic pathway in the development of anti‐neoplastic effects on breast remains unclear. Primary biologically active vitamin D hormone. The variation in the 5’‐promoter region of VDR gene can change the sequence of mRNA as well as protein levels, whereas alteration in 3’ UTR sequence can disturb the stability of mRNA thereby affecting the efficacy of translated protein. It should be advisable to perform dedicated studies about vitamin D levels in COVID-19 patients with different degrees of disease severity. It is a coactivator of the VDR, but it still needs 1,25D3. – May 2015, Microbiomes of both gut and airway are affected by Vitamin D and Vitamin D Receptor – Nov 2018, Prostate Cancer associated with various genes, including Vitamin D Receptor and CYP24A1 – Nov 2019, Restless Leg Syndrome linked to brain genes associated with Vitamin D and Iron – Nov 2019, Reduced muscle function in mice lacking Vitamin D Receptors in muscles – June 2019, Preterm birth 9 X more likely if fetus had a poor Vitamin D Receptor and previous miscarriage – Aug 2017, Cancer is leading cause of death - Vitamin D and Receptor activators help, Asthma 3.7X higher risk of poor Vitamin D Receptor (teens in Taiwan in this case) – Nov 2019, Melanoma cancer growth slowed by increased Vitamin D Receptor (yet again) – Oct 2019, Obesity 1.5 X more likely if poor Vitamin D Receptor – meta-analysis Nov 2019, Vitamin D deficiency is associated with 35 genes, only 7 of are commercially tested – Nov 2019, Prevent Osteoporosis and Have Strong Bones - book 2013, Increased risk of Osteoporosis if poor Vitamin D Receptor (UK males this time) – Sept 2019, Liver Cirrhosis death is 4X more likely if poor Vitamin D Receptor – Sept 2018, Asthma is 20 percent more likely with a poor Vitamin D Receptor gene – meta-analysis Oct 2019, Temporary hair loss (Telogen Effluvium) is 15X more likely if poor Vitamin D Receptor – Oct 2019, Breast cancer associated with Vitamin D Receptor (14th study) – Oct 2019, Hand, foot, and Mouth disease is 14X more likely if poor Vitamin D Receptor – Oct 2019, Non-alcoholic fatty liver disease and the Vitamin D Receptor – editorial Sept 2019, Leprosy risk is reduced by 3X for some types of Vitamin D Receptor (Brazil) – Sept 2019, Metabolic Syndrome 11X more likely if have a poor Vitamin D Receptor – 2018, Recurrent miscarriage occurs 2.2 more often if poor Vitamin D Receptor – Aug 2019, Osteoporosis 3X higher risk of in white men having a poor Vitamin D receptor – Aug 2019, Obesity associated with poor Vitamin D genes (VDR in this study) – Jan 2018, Osteoporosis is associated with genes such as the Vitamin D Receptor – July 2019, Colorectal Cancer risk increases when genes reduce the vitamin D levels – Aug 2019, Gastric Tissues and Vitamin D Genes – Aug 2019, Hypertension, Vitamin D, and Vitamin D Receptor – Aug 2019, Autoimmunity problems often associated with poor Vitamin D Receptors – March 2019, Many autoimmune diseases associated with low vitamin D or poor Vit D genes – July 2019, Cognitive decline not helped by daily vitamin D getting to just 30 ng – RCT July 2019, Vitamin D Receptor, the gut, the immune system, and the Middle East – May 2019, Vitamin D Receptor - activation and deactivation- self-hacked June 2019, MRSA Carriers not helped by 4,000 IU of Vitamin D (probably poor Vitamin D Receptor) – RCT Sept 2018, Adaptive and innate immune system, vitamin D genes, and Rheumatoid Arthritis – June 2019, TB patients had low Vitamin D and poor Vitamin D receptor – June 2019, Asthmatic children 5X more likely to have a poor Vitamin D Receptor – June 2019, Gestational Diabetes 2.4X more likely if poor Vitamin D Receptor (region in China) – June 2019, Mechanisms of vitamin D action in skeletal muscle – June 2019, Lumbar disc degeneration 30 percent more likely if poor Vitamin D Receptor – May 2019, Blood cell cancer is associated with a 3X worse Vitamin D Receptor – June 2019, Vitamin D Receptor described at US National Library of Medicine, Inflammatory bowel disease, gut bionome and Vitamin D Receptor – 2018, Lung Cancer more likely if poor Vitamin D Receptor – meta-analysis June 2019, TB and Leprosy are easily confused and associated with Vitamin D Receptor, Lyme disease appears to massively deactivate the Vitamin D Receptor - 2019, Best supplements for hay fever (Quercetin, which activates the Vitamin D receptor) - June 2019, After breast cancer treatment 4,000 IU of Vitamin D was not enough to help if have poor Vitamin D receptor – June 2019, Multiple Sclerosis and Vitamin D Receptor super enhancers – March 2019, Active Lupus associated with 3.8 X less activated Vitamin D Receptor – May 2019, Gestational Diabetes 3 X more likely if poor Vitamin D receptor (Turkey) – May 2019, U.S. healthcare system (and its investors) are really good at monetizing illness, but not wellness – May 2019, Vitamin D genes increase MS relapses in children by 2X – May 2019, Traumatic Brain Injury recovery helped by injection of 100,000 IU of Vitamin D – March 2019, Curcumin may increase Vitamin D in tissues (activates Vitamin D Receptor) – Dec 2010, Alzheimer’s is associated with all 7 of the genes which restrict vitamin D from getting to tissues – Sept 2018, Resveratrol prevented bone loss associated with T2DM (probably via VDR) – RCT Sept 2018, Effects of Resveratrol against Lung Cancer in mice – Nov 2017, Resveratrol Role in Autoimmune Disease-A Mini-Review.