Molecular Epidemiology of Non-Melanoma Skin Cancer

描述(申请人提供)：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，皮肤癌是一个了解癌症发生和环境诱发癌症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途径上，测试关于DNA修复基因和氧化应激解毒基因的多态的假设。展望未来，我们将继续建立在新汉普郡基于人群的大型病例对照研究的巨大现有资源的基础上(约1500例基底细胞癌(BCC)、1200例鳞状细胞癌(SCC)和1400例对照，主要调查者：卡拉加斯，CA57494)。在这一新的赠款期间，我们将把重点转向NMSC易感性的替代途径，重点放在免疫信号的作用上。紫外线辐射(UV)可引起局部和全身免疫抑制。我们将从免疫信号和炎症途径入手，解决NMSC的遗传易感性问题。这些发现将直接翻译到其他癌症和疾病过程中。这项应用旨在识别免疫信号通路中的遗传变异，从而提高皮肤癌的易感性。已识别的基因将有助于了解皮肤癌的预防以及其他具有很强免疫成分的疾病(即自身免疫性疾病和疫苗效力)。与公共卫生相关：紫外线辐射(UV)有充分的证据证明会导致局部和全身免疫抑制。这项应用旨在识别免疫信号通路中的遗传变异，从而提高皮肤癌的易感性。确定的基因将有助于了解皮肤癌的预防，以及其他具有很强免疫成分的疾病

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