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 3,566 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.© The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

authors

• Orlow, Irene
• Reiner, Anne S
• Thomas, Nancy E
• Roy, P K
• Kanetsky, Peter A
• Luo, Li
• Paine, Susan S
• Armstrong, Bruce K
• Kricker, Anne
• Marrett, Loraine D
• Rosso, Stefano
• Zanetti, Roberto
• Gruber, Stephen B
• Anton-Culver, Hoda
• Gallagher, Richard P
• Dwyer, Terence
• Busam, Klaus J
• Begg, Colin B
• Berwick, Marianne
• GEM Study Group

publication date

• October 2015

published in

• Carcinogenesis  Journal

Digital Object Identifier (DOI)

• https://doi.org/10.1093/carcin/bgv157

PubMed ID

• 26521212

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