Solar Exposure and Melanoma Survival

描述（由申请人提供）：令人惊讶的是，大量生态学证据表明，在地面紫外线辐射高的地区，黑色素瘤的预后更好。康涅狄格黑色素瘤队列的个体生存分析也表明，那些在高水平的阳光照射后患上黑色素瘤的人生存率更高。抗凋亡和抗增殖机制形成了对环境损害的防御，如紫外线辐射。然而，如果这些防御不能完全发挥作用，突变就会累积起来。维生素D受体受频繁紫外线照射刺激，具有抗凋亡和抗增殖作用。如果被诊断为黑色素瘤的人体内维生素D受体发生了变化，那么我们可以假设，我们会看到这些人体内的肿瘤更具侵袭性，存活率也更低，而那些发生了变化且日照时间较短的人存活率更低。利用GEM （1U01 CA 83180）的广泛资源，我们将在2500例新诊断的黑色素瘤病例中检验这一假设，该研究具有完整的数据和DNA收集。确定诊断时附近的环境紫外线照射和独立的估计终生阳光照射是否可以预测黑色素瘤患者在调整重要混杂因素（如癌症分期）后的生存率，如果是这样，这些影响是否独立于病变厚度，还是由病变厚度介导。2. 确定维生素D受体的功能多态性变异是否影响黑色素瘤的存活。3. 研究终身日照与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.