The interaction between vitamin D receptor polymorphisms and sun exposure around time of diagnosis influences melanoma survival.
Orlow I., Shi Y., Kanetsky PA., Thomas NE., Luo L., Corrales-Guerrero S., Cust AE., Sacchetto L., Zanetti R., Rosso S., Armstrong BK., Dwyer T., Venn A., Gallagher RP., Gruber SB., Marrett LD., Anton-Culver H., Busam K., Begg CB., Berwick M.
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.