Vitamin D receptor polymorphisms and survival in patients with cutaneous melanoma: a population-based study.
Carcinogenesis. 2015 Oct 31. pii: bgv157. [Epub ahead of print]
Orlow I, Reiner AS, Thomas NE1, Roy P, Kanetsky PA2, Luo L3, Paine S3, Armstrong BK4, Kricker A4, Marrett LD5, Rosso S6, Zanetti R6, Gruber SB7, Anton-Culver H8, Gallagher RP9, Dwyer T10, Busam K11, Begg CB, Berwick M3; GEM Study Group.
1Department of Dermatology, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27514, USA.
2Department of Cancer Epidemiology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL 33612, USA.
3Department of Internal Medicine, Epidemiology and Cancer Prevention, University of New Mexico, Albuquerque, NM 87131, USA.
4Sydney School of Public Health, The University of Sydney, Sydney, New South Wales 2006, Australia.
5Prevention and Cancer Control, Cancer Care Ontario, Toronto, Ontario M5G 2L7, Canada.
6Piedmont Cancer Registry, Centre for Epidemiology and Prevention in Oncology in Piedmont, Turin 10126, Italy.
7USC Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA 90033, USA.
8Department of Epidemiology, School of Medicine, University of California at Irvine, Irvine, CA 92617, USA.
9Cancer Control Research, British Columbia Cancer Research Centre, Vancouver, British Columbia V5Z 1L3, Canada.
10The George Institute for Global Health, Oxford Martin School, University of Oxford, Oxford OX1 3BD, UK and.
11Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
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 3566 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.
PMID: 26521212
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