Surprisingly, a great deal of ecological evidence shows that prognosis of melanoma is better in areas with high ground level ultraviolet radiation. An individual-level analysis of survival in a Connecticut melanoma cohort also shows that those who developed melanoma after high levels of sun exposure had better survival. Anti-apoptotic and anti-proliferative mechanisms form a defense against environmental damage, such as UV radiation. If these defenses are not fully functional, however, mutations will cumulate. The vitamin D receptor is stimulated by frequent UV exposure and it is anti-apoptotic and anti-proliferative. If there are alterations in the vitamin D receptor in individuals diagnosed with melanoma, then we would hypothesize that we would see more aggressive tumors and poor survival among those people, with even poorer survival among those with alterations and low sun exposure. Using the extensive resources of GEM (1U01 CA 83180), an international population-based study of melanoma with complete data and DNA collection, we will examine this hypothesis in 2500 newly diagnosed melanoma cases to: 1. Determine whether ambient UVR exposure near the time of diagnosis and, independently, estimated lifetime sun exposure predict survival from melanoma in individuals after adjusting for important confounders, such as cancer stage, and if so, whether these effects are independent of, or mediated by, lesion thickness. 2. Determine whether functional polymorphic variants in the vitamin D receptor affect survival from melanoma. 3. Investigate the interaction of lifetime solar exposure and polymorphisms in VDR and its effect on survival.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA112524-04
Application #
7409153
Study Section
Epidemiology of Cancer Study Section (EPIC)
Program Officer
Winn, Deborah M
Project Start
2005-05-06
Project End
2010-03-31
Budget Start
2008-04-01
Budget End
2009-03-31
Support Year
4
Fiscal Year
2008
Total Cost
$426,227
Indirect Cost
Name
University of New Mexico
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
868853094
City
Albuquerque
State
NM
Country
United States
Zip Code
87131
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Thomas, Nancy E; Edmiston, Sharon N; Kanetsky, Peter A et al. (2017) Associations of MC1R Genotype and Patient Phenotypes with BRAF and NRAS Mutations in Melanoma. J Invest Dermatol 137:2588-2598
Rodríguez, Vivian M; Berwick, Marianne; Hay, Jennifer L (2017) Communication about melanoma and risk reduction after melanoma diagnosis. Psychooncology 26:2142-2148
Orlow, Irene; Reiner, Anne S; Thomas, Nancy E et al. (2016) Vitamin D receptor polymorphisms and survival in patients with cutaneous melanoma: a population-based study. Carcinogenesis 37:30-8
Gibbs, David C; Orlow, Irene; Bramson, Jennifer I et al. (2016) Association of Interferon Regulatory Factor-4 Polymorphism rs12203592 With Divergent Melanoma Pathways. J Natl Cancer Inst 108:

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