Molecular Epidemiology of Non-Melanoma Skin Cancer

描述（由申请方提供）：非黑色素瘤皮肤癌（NMSC）是高加索人中最常见的恶性肿瘤。此外，皮肤癌是一个模型系统，用于了解致癌作用和遗传易感性的环境诱导的癌症。我们以前的遗传易感性的工作集中在致突变途径，测试有关DNA修复基因和氧化应激解毒基因多态性的假设。展望未来，我们将继续在新罕布什尔州一项大型基于人群的病例对照研究（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，CA 57494）的巨大现有资源的基础上再接再厉。在这个新的资助期内，我们将把重点转移到NMSC易感性的替代途径，重点是免疫信号的作用。紫外线辐射（UV）被充分证明可诱导局部和全身免疫抑制。我们将解决遗传易感性NMSC靶向免疫信号传导和炎症途径。这些发现将直接转化为其他癌症和疾病过程。该应用旨在识别免疫信号通路中的遗传变异，从而增强皮肤癌的易感性。识别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：紫外线辐射（UV）可诱导局部和全身免疫抑制。该应用旨在识别免疫信号通路中的遗传变异，从而增强皮肤癌的易感性。识别出的基因将有助于了解皮肤癌的预防，以及其他具有强烈免疫成分的疾病

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