Molecular Epidemiology of Non-Melanoma Skin Cancer

非黑色素瘤皮肤癌的分子流行病学

• 批准号: 6786055
• 负责人: HEATHER Hammond NELSON
• 金额: $ 42.29万
• 依托单位: HARVARD SCHOOL OF PUBLIC HEALTH
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-09-30 至 2007-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6786055
• 关键词: adult human (21+); basal cell carcinoma; biomarker; cancer risk; carcinogenesis; clinical research; disease /disorder etiology; disease /disorder onset; gene environment interaction; gene interaction; gene mutation; genetic polymorphism; genetic susceptibility; genotype; high risk behavior /lifestyle; human subject; immunocytochemistry; neoplasm /cancer genetics; oncoprotein p21; p53 gene /protein; patient oriented research; skin neoplasms; squamous cell carcinoma; sunburn; ultraviolet radiation

DESCRIPTION (provided by applicant): Non-melanoma skin cancer (NMSC) is the leading cancer diagnosis in the US. Although the mortality rate associated with NMSC is low, the very large and ever-increasing incidence translates into considerable morbidity and an appreciable number of deaths. In addition, considerable resources are necessary to treat over 1 million lesions each year. We have extended a large population based case-control study of nonmelanoma skin cancer in New Hampshire to include genetic susceptibility, and have identified several candidate genes that significantly interact with etiologic exposures to increase risk of NMSC. During the proposed study period we will expand this research to include a total of 1,375 BCC cases, 1,300 SCC cases and 1,500 controls. Importantly, we will also add two high-risk subgroups: early-onset and multiple BCC cases. Three areas of genetic susceptibility will be investigated: modification of UV exposure (MC1R and the glutatathione S-transfemses), DNA damage responsiveness (p53 and p21), and DNA repair proficiency (BER and NER genes). We will test for main gene effects between these polymorphisms and NMSC, as well as gene-environment interactions (i.e. sunburn history, ionizing radiation, and tanning bed use). Finally, given the central role of p53 in photocarcinogenesis, we will assess p53 status in case tumors using immunohistochemistry. We will investigate whether incorporating this biomarker of p53 alteration significantly improves disease classification and estimates of gene-environment interaction in NMSC.

描述(申请人提供)：非黑色素瘤皮肤癌(NMSC)是美国领先的癌症诊断。尽管与NMSC相关的死亡率很低，但非常大的发病率和不断增加的发病率转化为相当大的发病率和可观的死亡人数。此外，每年治疗100多万个皮损需要相当多的资源。我们在新罕布夏州扩展了一项基于大量人群的非黑色素瘤皮肤癌病例对照研究，包括遗传易感性，并确定了几个与病因暴露显著交互作用的候选基因，从而增加了NMSC的风险。在拟议的研究期间，我们将把这项研究扩大到包括1,375例基底细胞癌病例、1,300例鳞状细胞癌病例和1,500名对照病例。重要的是，我们还将增加两个高危亚组：早发性和多发性基底细胞癌病例。遗传易感性的三个方面将被调查：紫外线暴露的修饰(MC1R和谷氨酰胺S-Transfses)，DNA损伤反应(P53和p21)，以及DNA修复熟练程度(BER和NER基因)。我们将测试这些多态与NMSC之间的主要基因效应，以及基因与环境的交互作用(即晒伤病史、电离辐射和日光浴使用)。最后，鉴于P53在光癌发生中的中心作用，我们将使用免疫组织化学方法评估病例肿瘤中的P53状态。我们将调查纳入这种p53改变的生物标志物是否显著改善了NMSC的疾病分类和对基因-环境相互作用的估计。