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.

National Institute of Health (NIH)
National Cancer Institute (NCI)
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Epidemiology of Cancer Study Section (EPIC)
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Mikhail, Isis S
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University of New Mexico
Internal Medicine/Medicine
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United States
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Thomas, Nancy E; Edmiston, Sharon N; Orlow, Irene et al. (2018) Inherited Genetic Variants Associated with Melanoma BRAF/NRAS Subtypes. J Invest Dermatol 138:2398-2404
Orlow, Irene; Shi, Yang; Kanetsky, Peter A et al. (2018) The interaction between vitamin D receptor polymorphisms and sun exposure around time of diagnosis influences melanoma survival. Pigment Cell Melanoma Res 31:287-296
Gibbs, D C; Ward, S V; Orlow, I et al. (2017) Functional melanoma-risk variant IRF4 rs12203592 associated with Breslow thickness: a pooled international study of primary melanomas. Br J Dermatol 177:e180-e182
Vernali, Steven; Waxweiler, Weston T; Dillon, Patrick M et al. (2017) Association of Incident Amelanotic Melanoma With Phenotypic Characteristics, MC1R Status, and Prior Amelanotic Melanoma. JAMA Dermatol 153:1026-1031
Schwitzer, Emily; Orlow, Irene; Zabor, Emily C et al. (2017) No association between prediagnosis exercise and survival in patients with high-risk primary melanoma: A population-based study. Pigment Cell Melanoma Res 30:424-427
Mauguen, Audrey; Zabor, Emily C; Thomas, Nancy E et al. (2017) Defining Cancer Subtypes With Distinctive Etiologic Profiles: An Application to the Epidemiology of Melanoma. J Am Stat Assoc 112:54-63
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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