Melanoma death risk 0.63 X lower if poor Vitamin D Binding Gene – July 2023

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Association of functional, inherited vitamin D-binding protein variants with melanoma-specific death

JNCI Cancer Spectr . 2023 Jul 26;pkad051. doi: 10.1093/jncics/pkad051
David Corley Gibbs 1, Nancy E Thomas 2 3, Peter A Kanetsky 4, Li Luo 5, Klaus J Busam 6, Anne E Cust 7 8 9, Hoda Anton-Culver 10, Richard P Gallagher 11, Roberto Zanetti 12 13, Stefano Rosso 12 13, Lidia Sacchetto 12 13, Sharon N Edmiston 3, Kathleen Conway 3 14, David W Ollila 3 15, Colin B Begg 6, Marianne Berwick 5, Sarah V Ward 6 16, Irene Orlow 6

Background: It is unclear whether genetic variants affecting vitamin D metabolism are associated with melanoma prognosis. Two functional missense variants in the vitamin D-binding protein gene (GC), rs7041 and rs4588, determine three common haplotypes Gc1s, Gc1f, and Gc2. Gc1f may be associated with decreased all-cause death among melanoma patients, based on results of a prior study, but its association with melanoma-specific death is unclear.

Methods: We investigated the association of the Gc1s, Gc1f, and Gc2 haplotypes with melanoma-specific and all-cause death among 4,490 individuals with incident, invasive primary melanoma in two population-based studies using multivariable Cox-proportional hazards regression.

Results: In the pooled analysis of both datasets, those with the Gc1f haplotype had a 37% lower risk of melanoma-specific death compared to those without Gc1f (hazard ratio [HR] = 0.63, 95% confidence interval [CI] = 0.47 to 0.83, P = 0.001) adjusting for age, sex, study center, first or higher-order primary melanoma, tumor site, pigmentary phenotypes, and Breslow thickness. Associations were similar in both studies. In pooled analyses stratified by Breslow thickness, the corresponding melanoma-specific death HRs for those with the Gc1f haplotype compared to those without Gc1f were 0.89 (95% CI = 0.63 to 1.27) among participants with tumors ≤2.0 mm and 0.40 (95% CI = 0.25 to 0.63) among participants with tumors >2.0 mm (Pinteraction= 0.003).

Conclusions: Our findings suggest that individuals with the GC haplotype Gc1f may have a lower risk of dying from melanoma-specifically from thicker, higher-risk melanoma-compared to those without Gc1f.
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VitaminDWiki – Vitamin D Binding Protein category listing has 177 items

Vitamin D Binding Protein (GC) gene can decrease the bio-available Vitamin D that can get to cells,

• GC is not the only such gene - there are 3 others, all invisible to standard Vitamin D tests
• The bio-available calculation does not notice the effect of GC, CYP27B1, CYP24A1, and VDR
• The actual D getting to the cells is a function of measured D and all 4 genes
• There is >2X increase in 8+ health problems if have poor VDBP (GC)
• It appears that VDBP only blocks oral vitamin D,
  • but NOT Vitamin D from sun, UV, topical or inhaled (tissue activated)
  • A clue: - Vitamin D from UV is 2X better for MS than oral Vitamin D

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VitaminDWiki – Vitamin D Binding Protein has a list of health problems

Increased Risk	Health Problem
11 X	Preeclampsia
6.5X	T1D in SA Blacks
6 X	Food Allergy
5 X	PTSD
4 X, 5X	Kidney Cancer
4 X	Poor Response to Oral Vitamin D
3 X	Ear infection
2.8 X	MS
2 X	Colorectal Cancer
2 X	Prostate Cancer -in those with dark skins
1.3 X	Infertility

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Note: Other studies have found an INCREASE in cancer problems with Vitamin D Binding Protein

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16+ VitaminDWiki Vitamin D Binding gene with CANCER in the title

This list is automatically updated

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See also: Melanoma might be suppressed by Vitamin D - many studies

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