Impact of Genetic Polymorphisms on the Metabolic Pathway of Vitamin D and Survival in Non-Small Cell Lung Cancer
Nutrients 2021, 13(11), 3783; https://doi.org/10.3390/nu13113783
by Laura Elena Pineda Lancheros 1ORCID,Cristina Pérez Ramírez 1,2,*,Almudena Sánchez Martín 1,José María Gálvez Navas 1,2ORCID,Fernando Martínez Martínez 3,María del Carmen Ramírez Tortosa 2ORCID andAlberto Jiménez Morales 1
- 1 Pharmacy Service, Pharmacogenetics Unit, University Hospital Virgen de las Nieves, 18014 Granada, Spain
- 2 Center of Biomedical Research, Department of Biochemistry and Molecular Biology II, Institute of Nutrition, and Food Technology “José Mataix”, University of Granada, Avda. del Conocimiento s/n., 18016 Granada, Spain
- 3 Department of Pharmacy and Pharmaceutical Technology, Social and Legal Assistance Pharmacy Section, Faculty of Pharmacy, University of Granada, 18071 Granada, Spain
Vitamin D has been associated with risk, development, and progression of cancer. However, the genes involved in its metabolism are highly polymorphic, compromising its activity. The aim of this study is to evaluate the association between the gene polymorphisms involved in the metabolic pathway of vitamin D and survival in patients with non-small-cell lung cancer (NSCLC). The study was designed as an observational cohort which included 194 Caucasians patients from southern Spain with NSCLC. Real-time polymerase chain reaction was used to analyze the following polymorphisms:
- CYP27B1 rs4646536, rs3782130, and rs10877012;
- CYP24A1 rs6068816 and rs4809957; GC rs7041;
- CYP2R1 rs10741657;
- VDR rs1544410 (BsmI), rs11568820 (Cdx-2), rs2228570 (FokI), rs7975232 (ApaI), and rs731236 (TaqI).
Progression-free survival (PFS) and overall survival were assessed. Cox regression showed that rs4646536 was associated with PFS in the general population (p = 0.0233) and in the non-resected NSCLC subgroup (p = 0.0233). In the resected NSCLC subgroup, rs11568820 was associated with OS (p = 0.0129) and rs7041 with PFS (p = 0.0447). In the non-resected NSCLC subgroup, rs6068816 was associated with PFS (p = 0.0048) and OS (p = 0.0089) and rs731236 and rs7975232 were associated with OS (p = 0.0005) and PFS (p = 0.0002), respectively. The other polymorphisms showed no effect on the results. The rs4646536, rs6068816, rs7041, rs11568820, rs731236, and rs7975232 polymorphisms are associated with survival in NSCLC and may have a substantial role as prognostic markers of the disease.
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Lung Cancer and Vitamin D Receptor
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- Lung Cancer risk increases if low Vitamin D, poor activation of Vitamin D Receptor which affects the CALB1 gene – June 2024
- Lung Cancer is up to 7 X more deadly if poor vitamin D genes – Oct 2021
- Lung Cancer more likely if poor Vitamin D Receptor – meta-analysis June 2019
- Effects of Resveratrol against Lung Cancer in mice – Nov 2017
- Lung Cancer patients were 2.4 times more likely to have a poor Vitamin D Receptor gene – July 2017
Some Lung Cancer and other gene studies
- Lung Cancer (NSLC) more lethal if poor Vitamin D gene ( CYP2R1) – Oct 2019
- Live longer with lung cancer if have good vitamin D genes (or perhaps lots of vitamin D) – Dec 2017
- Lung cancer – reduced deaths if have a good vitamin D gene (CYP27B1) – Feb 2015
- Lung cancer not reduced when vitamin D levels were less than 40 ng – June 2011
- Higher levels of vitamin D needed to get past the poor gene restirctions
Cancers and CPY24A1
Cancers might alter CYP24A1 gene
CYP24B1 and gene chart
CYP27B1 category listing contains the following
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
Vitamin D blood test misses CYP27B1 and other genes
Vitamin D Binding Protein (GC)
Vitamin D Binding Protein category listing has178 items along with related searches
Vitamin D Receptor pages with CANCER in title (75 as of Oct 2021)
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Items found: 90
Vitamin D Receptor - # of diseases, how to fix a poor VDR
The risk of 44 diseases at least double with poor Vitamin D Receptor as of Oct 2019
Vitamin D Receptor activation can be increased by any of: Resveratrol, Omega-3, Magnesium, Zinc, Quercetin, non-daily Vit D, Curcumin, intense exercise, Ginger, Essential oils, etc Note: The founder of VitaminDWiki uses 10 of the 13 known VDR activators
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