Table of contents
The vitamin D receptor gene as a determinant of survival in pancreatic cancer patients: Genomic analysis and experimental validation.
PLoS One. 2018 Aug 14;13(8):e0202272. doi: 10.1371/journal.pone.0202272. eCollection 2018.
Innocenti F1, Owzar K2,3, Jiang C3, Etheridge AS1, Gordân R2, Sibley AB3, Mulkey F3, Niedzwiecki D3, Glubb D1, Neel N1, Talamonti MS4, Bentrem DJ5, Seiser E1, Yeh JJ1, Van Loon K6, McLeod H7, Ratain MJ8, Kindler HL8, Venook AP6, Nakamura Y8, Kubo M9, Petersen GM10, Bamlet WR10, McWilliams RR10.
Advanced pancreatic cancer is a highly refractory disease almost always associated with survival of little more than a year. New interventions based on novel targets are needed. We aim to identify new genetic determinants of overall survival (OS) in patients after treatment with gemcitabine using genome-wide screens of germline DNA. We aim also to support these findings with in vitro functional analysis.
PATIENTS AND METHODS:
Genome-wide screens of germline DNA in two independent cohorts of pancreatic cancer patients (from the Cancer and Leukemia Group B (CALGB) 80303 and the Mayo Clinic) were used to select new genes associated with OS. The vitamin D receptor gene (VDR) was selected, and the interactions of genetic variation in VDR with circulating vitamin D levels and gemcitabine treatment were evaluated. Functional effects of common VDR variants were also evaluated in experimental assays in human cell lines.
The rs2853564 variant in VDR was associated with OS in patients from both the
- Mayo Clinic (HR 0.81, 95% CI 0.70-0.94, p = 0.0059) and
- CALGB 80303 (HR 0.74, 0.63-0.87, p = 0.0002).
rs2853564 interacted with high pre-treatment levels of 25-hydroxyvitamin D (25(OH)D, a measure of endogenous vitamin D) (p = 0.0079 for interaction) and with gemcitabine treatment (p = 0.024 for interaction) to confer increased OS. rs2853564 increased transcriptional activity in luciferase assays and reduced the binding of the IRF4 transcription factor.
Our findings propose VDR as a novel determinant of survival in advanced pancreatic cancer patients. Common functional variation in this gene might interact with endogenous vitamin D and gemcitabine treatment to determine improved patient survival. These results support evidence for a modulatory role of the vitamin D pathway for the survival of advanced pancreatic cancer patients.
Plasma 25-hydroxyvitamin D levels, vitamin D intake, and pancreatic cancer risk or mortality: a meta-analysis
Oncotarget. 2017 Jun 29. doi: 10.18632/oncotarget.18888.
Zhang X1, Huang XZ1, Chen WJ1, Wu J1, Chen Y2, Wu CC1, Wang ZN3.
21% reduction in deaths, but no reduction in occurrence (study on this page)
That is, high Vitamin D blood level does not change who gets pancreatic caner, but it does increase survival
Note: Like many other diseases, how much vitamin D actually gets to the cells is far more important that how much is in blood
- Pancreatic Cancer massively deregulates the local Vitamin D receptors and CPY24A1 – July 2014
- Restoring vitamin D levels to Pancreatic patients required up to 20000 IU daily – May 2012
Note: Probably need a lot more vitamin D to get past deregulated Vitamin D Receptor
- Pancreatic Cancer Survival 40 percent more likely if had adequate vitamin D (30 ng) – June 2016 -vs. the 21% increased survival in the meta-analysis
Vitamin D Receptor category has the following
Vitamin D tests cannot detect Vitamin D Receptor (VDR) problems
A poor VDR restricts Vitamin D from getting in the cells
It appears that 30% of the population has a poor VDR (40% of the Obese )
A poor VDR increases the risk of 52 health problems click here for details
VDR at-home test $29 - results not easily understood in 2016
There are hints that you may have inherited a poor VDR
Compensate for poor VDR by increasing one or more:
|1) Vitamin D supplement|
Sun, Ultraviolet -B
| Vitamin D in the blood |
and thus to the cells
|2) Magnesium||Vitamin D in the blood |
AND to the cells
|3) Omega-3||Vitamin D to the cells|
|4) Resveratrol||Vitamin D to the cells|
|5) Intense exercise||Vitamin D Receptor|
|6) Get prescription for VDR activator|
|Vitamin D Receptor|
|7) Quercetin (flavonoid)||Vitamin D Receptor|
|8) Zinc is in the VDR||Vitamin D Receptor|
|9) Boron||Vitamin D Receptor ?, |
|10) Essential oils e.g. ginger, curcumin||Vitamin D Receptor|
|11) Progesterone||Vitamin D Receptor|
Note: If you are not feeling enough benefit from Vitamin D, you might try increasing VDR activation.
You might feel the benefit within days of adding one or more of the above
Far healthier and stronger at age 72 due to supplements Includes 6 supplements which help the VDR
Genetics category listing contains the following
Vitamin D blood test misses a lot
- Snapshot of the literature by VitaminDWiki - (subject to many future developments)
- Vitamin D from coming from tissues (vs blood) was speculated to be 50% in 2014, andi in 2017 is speculated to be 90%
- Note: Good results from a blood test (> 40 ng) does not mean that a good amount of Vitamin D actually gets to cells
- A Vitamin D test in cells appears feasible (personal communication)
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 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
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&4
The associations between vitamin D status, including plasma 25-hydroxyvitamin D [25(OH)D] levels and vitamin D intake, and pancreatic cancer risk and mortality are inconsistent. The aims of this study are to evaluate the antitumor and therapeutic effects of vitamin D status for pancreatic cancer patients.
A literature search for relevant studies was conducted using PubMed and Embase databases. Risk ratio (RR), hazard ratio (HR), and 95% confidence interval (CI) were used as the effect measures. All statistical analyses were performed using Stata software 12.0.
Our results indicated that high plasma 25(OH)D levels were inversely associated with pancreatic cancer mortality without significant heterogeneity (HR=0.81, 95% CI=0.68-0.96). However, high plasma 25(OH)D levels could not reduce pancreatic cancer risk (RR=1.02, 95% CI=0.66-1.57). Moreover, vitamin D intake was also not associated with pancreatic cancer risk (RR=1.11, 95% CI=0.67-1.86)
Conclusions: Our results indicate that high plasma 25(OH)D levels were significantly associated with improved survival in pancreatic cancer patients. However, there were no significant associations between vitamin D intake or plasma 25(OH)D levels and pancreatic cancer risk.
PMID: 28733547 DOI: 10.18632/oncotarget.18888
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