Solar Exposure and Melanoma Survival

阳光照射和黑色素瘤存活率

基本信息

批准号：
7590481
负责人：
MARIANNE BERWICK
金额：
$ 41.31万
依托单位：
UNIVERSITY OF NEW MEXICO
依托单位国家：
美国
项目类别：
财政年份：
2005
资助国家：
美国
起止时间：
2005-05-06 至 2012-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7590481
关键词：
Accounting Address Affect American Joint Committee on Cancer Apoptotic Area Australia Behavior Breslow Thickness CDKN2A gene Canada Case-Control Studies Cessation of life Collaborations Collection Connecticut Cutaneous Melanoma DNA DNA Databases DNA Library Data Death Rate Developed Countries Developing Countries Development Diagnosis Diagnostic Neoplasm Staging Disease Enrollment Environment Exposure to Genes Genetic Genetic Polymorphism Genotype Geographic Locations Goals Hereditary Melanoma Incidence Individual International Interview Italy Lesion Location Measures Mediating Memorial Sloan-Kettering Cancer Center Mexico Mutation Newly Diagnosed Nucleotide Excision Repair Occupational Exposure Participant Patients Pigmentation physiologic function Poly A Population Principal Investigator Receptor Gene Recording of previous events Research Resources S-Phase Fraction Skin Cancer Solar elastosis Staging Sun Exposure Survival Analysis Testing Thick Time UV Radiation Exposure Ulcer Ultraviolet B Radiation Ultraviolet Rays United States Universities Variant Vital Status Vitamin D Vitamin D3 Receptor Vitamins Weight cohort experience follow-up improved melanoma mortality novel outcome forecast population based prevent programs receptor response tumor

项目摘要

DESCRIPTION (provided by applicant): 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.

描述（由申请人提供）：令人惊讶的是，大量的生态证据表明，在较高的紫外线辐射的地区，黑色素瘤的预后更好。康涅狄格黑色素瘤队列中生存的个体水平分析还表明，在高水平的阳光暴露后发展黑色素瘤的人的生存更好。抗凋亡和抗增殖机制构成了针对环境破坏的防御，例如紫外线辐射。但是，如果这些防御能力不完全，突变将累积。维生素D受体受到频繁暴露的刺激，并且是抗凋亡和抗增殖性的。如果在被诊断出患有黑色素瘤的个体中维生素D受体发生了变化，那么我们假设我们会看到这些人的侵略性肿瘤和生存率较差，而在有改变和阳光暴露低的人中，生存率较差。使用GEM（1U01 CA 83180），一项基于国际人群的黑色素瘤研究和收集DNA的大量资源，我们将在2500例新诊断的黑色素瘤病例中研究这一假设，以下是：1。确定在诊断期附近的周围UVR暴露在诊断期附近，并独立于估计的生存期间的生存阶段以及是否能够估计，该疾病是否会在癌症中造成癌症的生存，是否适用于酸性阶段，是否适用于酸性疾病。病变厚度的或介导。 2。确定维生素D受体中的功能多态性变异是否会影响黑色素瘤的存活。 3。研究VDR中寿命太阳暴露和多态性的相互作用及其对生存的影响。