Solar Exposure and Melanoma Survival

描述（由申请人提供）：令人惊讶的是，大量的生态证据表明，黑色素瘤的预后在地面紫外线辐射高的地区更好。康涅狄格州黑色素瘤队列的个体水平生存分析也表明，那些在高水平阳光照射后患黑色素瘤的人生存率更高。抗细胞凋亡和抗增殖机制形成对环境损伤（例如UV辐射）的防御。然而，如果这些防御功能不全，突变就会累积。维生素D受体被频繁的紫外线照射所刺激，并且具有抗凋亡和抗增殖的作用。如果在诊断为黑色素瘤的个体中维生素D受体发生了改变，那么我们会假设我们会看到这些人中更具侵袭性的肿瘤和较差的生存率，在那些有改变和低阳光照射的人中生存率更差。利用GEM（1U01 CA 83180）的广泛资源，一项具有完整数据和DNA收集的国际人群为基础的黑色素瘤研究，我们将在2500例新诊断的黑色素瘤病例中检验这一假设，以：1。确定是否周围的紫外线辐射暴露的诊断时间附近，独立地，估计一生的阳光照射预测生存黑色素瘤的个人后，调整重要的混杂因素，如癌症阶段，如果是这样，这些影响是否是独立的，或介导的，病变厚度。2.确定维生素D受体的功能多态性变体是否影响黑色素瘤的生存率。3.研究太阳照射与VDR多态性的相互作用及其对生存的影响。

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.