Molecular Epidemiology of Non-Melanoma Skin Cancer

描述（由申请人提供）：非黑色素瘤皮肤癌（NMSC）是白种人中最常见的恶性肿瘤。此外，皮肤癌是了解环境诱发癌症的致癌和遗传易感性的模型系统。我们之前在遗传易感性方面的工作主要集中在致突变性途径上，测试DNA修复基因和氧化应激解毒基因多态性的假设。展望未来，我们将继续建立在新罕布什尔州一项大型基于人群的病例对照研究的巨大现有资源上（大约1500例基底细胞癌（BCC）， 1200例鳞状细胞癌（SCC）和1400例对照，主要研究者：Karagas， CA57494）。在这个新的资助期，我们将把重点转移到NMSC易感性的替代途径上，重点关注免疫信号的作用。紫外线辐射（UV）可以引起局部和全身的免疫抑制。我们将研究针对免疫信号和炎症途径的NMSC的遗传易感性。这些发现将直接转化为其他癌症和疾病的过程。本应用程序旨在确定免疫信号通路的遗传变异，增强对皮肤癌的易感性。确定的基因将有助于了解皮肤癌的预防，以及其他具有强免疫成分的疾病（即自身免疫性疾病和疫苗效率）。公共卫生相关性：有充分证据表明，紫外线辐射（UV）可诱导局部和全身免疫抑制。本应用程序旨在确定免疫信号通路的遗传变异，增强对皮肤癌的易感性。确定的基因将有助于了解皮肤癌的预防，以及其他具有强免疫成分的疾病

DESCRIPTION (provided by applicant): Non-melanoma skin cancers (NMSC) are the most prevalent malignancies among Caucasians. Further, skin cancer is a model system for understanding carcinogenesis and genetic susceptibility to environmentally-induced cancers. Our prior work on genetic susceptibility has focused on mutagenicity pathways, testing hypotheses regarding polymorphisms in DNA repair genes and genes in oxidative stress detoxification. Moving forward, we will continue to build on the tremendous existing resource of a large population-based case control study in New Hampshire (approximately 1500 basal cell carcinoma (BCC), 1200 squamous cell carcinoma (SCC) and 1400 controls, principal investigator: Karagas, CA57494). In this new grant period we will shift our focus to alternative pathways of susceptibility in NMSC, focusing on the role of immune signaling. Ultraviolet radiation (UV) is well documented to induce local and systemic immunosuppression. We will address genetic susceptibility to NMSC targeting immune signaling and inflammation pathways. These findings will be directly translatable to other cancers and disease processes. This application aims to identify genetic variation in immune signaling pathways that enhances susceptibility to skin cancer. Identified genes would be useful in understanding skin cancer prevention, as well as other diseases with a strong immune component (i.e. autoimmune disease and vaccine efficiency). PUBLIC HEALTH RELEVANCE: Ultraviolet radiation (UV) is well documented to induce local and systemic immunosuppression. This application aims to identify genetic variation in immune signaling pathways that enhances susceptibility to skin cancer. Identified genes would be useful in understanding skin cancer prevention, as well as other diseases with a strong immune component