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

• Published in: Pigment cell and melanoma research Vol. 31; no. 2; pp. 287 - 296
• Main 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, Roy, Pampa, Patel, Himali, Yoo, Sarah, Reiner, Anne, Paine, Susan, Kricker, Anne, Tucker, Paul, From, Lynn, Ollila, David W., Groben, Pamela A., Rebbeck, Timothy R., Taylor, Julia Lee, Madronich, Sasha
• Format: Journal Article
• Language: English
• Published: England Wiley Subscription Services, Inc 01.03.2018
• Subjects: Diagnosis; Exposure; Female; Genetic Predisposition to Disease; haplotype; Haplotypes; Haplotypes - genetics; Humans; interaction; Male; Melanoma; Melanoma - diagnosis; Melanoma - genetics; Melanoma - pathology; polymorphism; Polymorphism, Single Nucleotide - genetics; Receptors, Calcitriol - genetics; Regression analysis; Regression models; Risk Factors; Single-nucleotide polymorphism; SNP; Statistical analysis; Sun; Sunlight - adverse effects; Survival; Survival Analysis; Ultraviolet radiation; UVB; Vitamin D; vitamin D receptor; Vitamin D receptors; UVB; haplotype; SNP; exposure; survival; interaction; melanoma; polymorphism; vitamin D receptor
• ISSN: 1755-1471; 1755-148X
• DOI: 10.1111/pcmr.12653

Summary 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.