Title: The interaction between vitamin D receptor polymorphisms and sun exposure around time of diagnosis influences melanoma survival.

Authors: Orlow, Irene; Shi, Yang; Kanetsky, Peter A; Thomas, Nancy E; Luo, Li; Corrales-Guerrero, Sergio; Cust, Anne E; Sacchetto, Lidia; Zanetti, Roberto; Rosso, Stefano; Armstrong, Bruce K; Dwyer, Terence; Venn, Alison; Gallagher, Richard P; Gruber, Stephen B; Marrett, Loraine D; Anton-Culver, Hoda; Busam, Klaus; Begg, Colin B; Berwick, Marianne; GEM Study Group

Published In Pigment Cell Melanoma Res, (2018 Mar)

Abstract: Evidence on the relationship between the vitamin D pathway and outcomes in melanoma is growing, although it is not always clear. We investigated the impact of measured levels of sun exposure at diagnosis on associations of vitamin D receptor gene (VDR) polymorphisms and melanoma death in 3336 incident primary melanoma cases. Interactions between six SNPs and a common 3'-end haplotype were significant (p < .05). These SNPs, and a haplotype, had a statistically significant association with survival among subjects exposed to high UVB in multivariable regression models and exerted their effect in the opposite direction among those with low UVB. SNPs rs1544410/BsmI and rs731236/TaqI remained significant after adjustment for multiple testing. These results suggest that the association between VDR and melanoma-specific survival is modified by sun exposure around diagnosis, and require validation in an independent study. Whether the observed effects are dependent or independent of vitamin D activation remains to be determined.

PubMed ID: 28990310

MeSH Terms: Female; Genetic Predisposition to Disease*; Haplotypes/genetics; Humans; Male; Melanoma/diagnosis*; Melanoma/genetics*; Melanoma/pathology; Polymorphism, Single Nucleotide/genetics*; Receptors, Calcitriol/genetics*; Risk Factors; Sunlight/adverse effects*; Survival Analysis