Molecular Epidemiology of Non-Melanoma Skin Cancer

描述（由申请人提供）：非黑色素瘤皮肤癌（NMSC）是美国主要的癌症诊断。虽然与NMSC相关的死亡率较低，但非常大且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，每年需要相当多的资源来治疗超过100万个病变。我们在新罕布什尔州扩展了一项基于大规模人群的非黑色素瘤皮肤癌病例对照研究，纳入了遗传易感性，并确定了几个与病因暴露显著相互作用的候选基因，以增加NMSC的风险。在拟议的研究期间，我们将扩大这项研究，包括总共1,375例BCC病例，1,300例SCC病例和1,500例对照。重要的是，我们还将增加两个高危亚组：早发性和多发性BCC病例。将研究遗传易感性的三个领域：紫外线暴露的修饰（MC 1 R和谷胱甘肽S-转移酶），DNA损伤反应（p53和p21）和DNA修复能力（BER和NER基因）。我们将测试这些多态性和NMSC之间的主要基因效应，以及基因-环境相互作用（即晒伤史，电离辐射和晒黑床使用）。最后，鉴于p53在光致癌作用中的核心作用，我们将使用免疫组化评估肿瘤中p53的状态。我们将研究是否纳入p53改变的生物标志物显着改善疾病分类和NMSC中基因-环境相互作用的估计。

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.