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Vitamin D receptor polymorphisms and survival in patients with cutaneous melanoma: a population-based study.

ABSTRACT: Factors known to affect melanoma survival include age at presentation, sex and tumor characteristics. Polymorphisms also appear to modulate survival following diagnosis. Result from other studies suggest that vitamin D receptor (VDR) polymorphisms (SNPs) impact survival in patients with glioma, renal cell carcinoma, lung, breast, prostate and other cancers; however, a comprehensive study of VDR polymorphisms and melanoma-specific survival is lacking. We aimed to investigate whether VDR genetic variation influences survival in patients with cutaneous melanoma. The analysis involved 3566 incident single and multiple primary melanoma cases enrolled in the international population-based Genes, Environment, and Melanoma Study. Melanoma-specific survival outcomes were calculated for each of 38 VDR SNPs using a competing risk analysis after adjustment for covariates. There were 254 (7.1%) deaths due to melanoma during the median 7.6 years follow-up period. VDR SNPs rs7299460, rs3782905, rs2239182, rs12370156, rs2238140, rs7305032, rs1544410 (BsmI) and rs731236 (TaqI) each had a statistically significant (trend P values < 0.05) association with melanoma-specific survival in multivariate analysis. One functional SNP (rs2239182) remained significant after adjustment for multiple testing using the Monte Carlo method. None of the SNPs associated with survival were significantly associated with Breslow thickness, ulceration or mitosis. These results suggest that the VDR gene may influence survival from melanoma, although the mechanism by which VDR exerts its effect does not seem driven by tumor aggressiveness. Further investigations are needed to confirm our results and to understand the relationship between VDR and survival in the combined context of tumor and host characteristics.

SUBMITTER: Orlow I

PROVIDER: S-EPMC4715233 | biostudies-literature | 2016 Jan

REPOSITORIES: biostudies-literature

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Vitamin D receptor polymorphisms and survival in patients with cutaneous melanoma: a population-based study.

Orlow Irene I Reiner Anne S AS Thomas Nancy E NE Roy Pampa P Kanetsky Peter A PA Luo Li L Paine Susan S Armstrong Bruce K BK Kricker Anne A Marrett Loraine D LD Rosso Stefano S Zanetti Roberto R Gruber Stephen B SB Anton-Culver Hoda H Gallagher Richard P RP Dwyer Terence T Busam Klaus K Begg Colin B CB Berwick Marianne M

Carcinogenesis 20151031 1

Factors known to affect melanoma survival include age at presentation, sex and tumor characteristics. Polymorphisms also appear to modulate survival following diagnosis. Result from other studies suggest that vitamin D receptor (VDR) polymorphisms (SNPs) impact survival in patients with glioma, renal cell carcinoma, lung, breast, prostate and other cancers; however, a comprehensive study of VDR polymorphisms and melanoma-specific survival is lacking. We aimed to investigate whether VDR genetic v ...[more]

PMID: 26521212

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Project description:Objective: Vitamin D receptor (VDR) mediates vitamin D activity. We examined whether VDR expression in excised melanoma tissues is associated with VDR gene (VDR) polymorphisms.Methods: We evaluated VDR protein expression (by monoclonal antibody immunostaining), melanoma characteristics, and carriage of VDR-FokI-rs2228570 (C>T),VDR-BsmI-rs1544410 (G>A),VDR-ApaI-rs7975232 (T>G), andVDR-TaqI-rs731236 (T>C) polymorphisms (by restriction fragment length polymorphism). Absence or presence of restriction site was denoted by a capital or lower letter, respectively: " F" and " f" for FokI, " B" and " b" for BsmI, " A" and " a" for ApaI, and " T" and " t" for TaqI endonuclease. Seventy-four Italian cutaneous primary melanomas (52.1±12.7 years old) were studied; 51.4% were stage I, 21.6% stage II, 13.5% stage III, and 13.5% stage IV melanomas. VDR expression was categorized as follows: 100% positivevs. <100%; over the median 20% (high VDR expression) vs. ≤20% (low VDR expression); absence vs. presence of VDR-expressing cells.Results: Stage I melanomas, Breslow thickness of <1.00 mm, level II Clark invasion, Aa heterozygous genotype, and AaTT combined genotype were more frequent in melanomas with high vs. low VDR expression. Combined genotypes BbAA, bbAa, AATt, BbAATt, and bbAaTT were more frequent in 100% vs. <100% VDR-expressing cells. Combined genotype AATT was more frequent in melanomas lacking VDR expression (odds ratio=14.5; P=0.025). VDR expression was not associated with metastasis, ulceration, mitosis >1, regression, tumor-infiltrating lymphocytes, tumoral infiltration of vascular tissues, additional skin and non-skin cancers, and melanoma familiarity.Conclusions: We highlighted that VDR polymorphisms can affect VDR expression in excised melanoma cells. Low VDR expression in AATT carriers is a new finding that merits further study. VDR expression possibly poses implications for vitamin D supplementation against melanoma. VDR expression and VDR genotype may become precise medicinal tools for melanoma in the future.

Dataset Information

Vitamin D receptor polymorphisms and survival in patients with cutaneous melanoma: a population-based study.

Publications

Vitamin D receptor polymorphisms and survival in patients with cutaneous melanoma: a population-based study.

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