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

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

doi:10.1111/pcmr.12653

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

Pigment Cell Melanoma Res. 2018 Mar;31(2):287-296. doi: 10.1111/pcmr.12653. Epub 2017 Nov 5.

Authors

Irene Orlow¹, Yang Shi², Peter A Kanetsky³, Nancy E Thomas⁴, Li Luo⁵, Sergio Corrales-Guerrero¹, Anne E Cust⁶, Lidia Sacchetto⁷, Roberto Zanetti⁷, Stefano Rosso⁷, Bruce K Armstrong⁸, Terence Dwyer⁹, Alison Venn¹⁰, Richard P Gallagher¹¹, Stephen B Gruber¹², Loraine D Marrett¹³, Hoda Anton-Culver¹⁴, Klaus Busam¹⁵, Colin B Begg¹, Marianne Berwick⁵; GEM Study Group⁵

Collaborators

GEM Study Group:
Pampa Roy, Himali Patel, Sarah Yoo, Anne Reiner, Susan Paine, Anne Kricker, Paul Tucker, Lynn From, David W Ollila, Pamela A Groben, Timothy R Rebbeck, Julia Lee Taylor, Sasha Madronich

Affiliations

¹ Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
² Biostatistics Shared Resource, University of New Mexico Comprehensive Cancer Center, Albuquerque, NM, USA.
³ Department of Cancer Epidemiology, Moffitt Cancer Center, Tampa, FL, USA.
⁴ Department of Dermatology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
⁵ Department of Internal Medicine, Division of Epidemiology, Biostatistics and Preventive Medicine, University of New Mexico Comprehensive Cancer Center, University of New Mexico, Albuquerque, NM, USA.
⁶ Cancer Epidemiology and Prevention Research, Sydney School of Public Health, The University of Sydney, Camperdown, NSW, Australia.
⁷ Piedmont Cancer Registry, Centre for Epidemiology and Prevention in Oncology in Piedmont, Turin, Italy.
⁸ School of Global and Population Health, The University of Western Australia, Perth, WA, Australia.
⁹ Nuffield Department of Obstetrics and Gynecology, The George Institute for Global Health, University of Oxford, Oxford, UK.
¹⁰ Menzies Institute for Medical Research, University of Tasmania, Hobart, TAS, Australia.
¹¹ Cancer Control Research, British Columbia Cancer Research Centre, Vancouver, BC, Canada.
¹² USC Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, USA.
¹³ Prevention and Cancer Control, Cancer Care Ontario, Toronto, ON, Canada.
¹⁴ Department of Epidemiology, School of Medicine, University of California at Irvine, Irvine, CA, USA.
¹⁵ Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.

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.

Keywords: SNP; UVB; exposure; haplotype; interaction; melanoma; polymorphism; survival; vitamin D receptor.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

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

Substances

Receptors, Calcitriol
VDR protein, human

Abstract

Publication types

MeSH terms

Substances

Grants and funding