Solar Exposure and Melanoma Survival

描述(申请人提供)：令人惊讶的是，大量生态学证据表明，在地面紫外线辐射较高的地区，黑色素瘤的预后较好。康涅狄格州黑色素瘤队列中的个体水平的生存分析也表明，那些在高水平日晒后患上黑色素瘤的人生存得更好。抗凋亡和抗增殖机制形成了对环境破坏的防御，如紫外线辐射。然而，如果这些防御不是完全起作用的，突变就会累积。维生素D受体受到频繁的紫外线照射的刺激，具有抗凋亡和抗增殖的作用。如果被诊断为黑色素瘤的人的维生素D受体发生了变化，那么我们会假设，在这些人中，我们会看到更具侵袭性的肿瘤和较差的存活率，而那些有变化和低日晒的人的存活率甚至更低。利用GEM(1U01 CA 83180)的广泛资源，我们将在2 500例新诊断的黑色素瘤病例中检验这一假设：1.在调整了重要的混杂因素(如癌症分期)后，确定接近诊断时的环境紫外线照射和独立的终身估计日晒是否可以预测个体黑色素瘤的生存率，如果是这样，这些影响是否独立于皮损厚度或由皮损厚度介导。2.确定维生素D受体的功能性多态变异是否会影响黑色素瘤的存活率。3.研究终生日照暴露与VDR基因多态性的交互作用及其对存活率的影响。

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.