DNA REPAIR AND CHROMOSOME INSTABILITY IN SKIN CANCERS

基底细胞癌和鳞状细胞癌(BCC和SCC)通常发生在 暴露的部位，如头部和颈部，通常是由于慢性 暴露于太阳紫外线辐射(UVR)。主持人的角色 对紫外线致癌的敏感性在两个国家都没有很好的定义 分子或细胞遗传学水平。我们建议进行病例对照 紫外线辐射遗传易感性的研究 (定义为DNA修复能力下降或诱变剂敏感性增加) 以及皮肤癌的发展和进展。DNA修复 容量将通过宿主细胞再激活试验和UV- 受辐射的质粒组。诱变剂敏感度将通过UVR诱导 染色体断裂和染色体上断裂部位的频率。我们 将使用300例未经治疗的患者的外周血淋巴细胞(150例基底细胞癌和 150个SCC)和300个对照来执行这些检测。的具体目标 这项建议是：(1)检查DNA修复与 能力和皮肤癌的发展，(2)检查 诱变剂敏感性与皮肤发育的关系 癌，以及(3)。来考察两种疾病之间的联系 染色体上的断裂部位与皮肤的发育和进展 癌症，以及(4)评估DNA修复能力与 诱变剂敏感性，染色体断裂部位的频率，基因突变， 以及流行病学和临床变量，如阳光暴露 病史、临床分期和治疗结果。我们会 研究这两种遗传易感性之间的关系 标记物与皮肤癌发生发展与表型的关系 性格、家族史、阳光和其他致癌暴露， Ras癌基因和p53抑癌基因突变频率的研究 肿瘤的临床分期和进展(由Core B收集；Dr. 玛格丽特·斯皮茨、兰德尔·韦伯和Honnavara Ananthaswamy)和治疗 结果(由Scott Lippman和Ruben Lotan博士衡量) 同样的主题。这项研究将提供有关公用事业的信息 这些遗传易感性的标记在识别个体时 患皮肤癌的风险很高。

Basal cell and squamous cell carcinomas (BCC and SCC) commonly occur on exposed sites such as the head and neck and are usually due to chronic exposure to solar ultraviolet radiations (UVR). The role of host susceptibility to UVR carcinogenesis is not well defined at either the molecular or cytogenetic level. We propose to conduct a case- control study to evaluate the association between genetic susceptibility to UVR (defined as decreased DNA repair capacity or increased mutagen sensitivity) and the development and progression of skin carcinomas. The DNA repair capacity will be measured by host-cell reactivation assay with UV- irradiated plasmids. Mutagen sensitivity will be measured by UVR induced chromosomal breaks and the frequency of break sites on chromosomes. We will use peripheral blood lymphocytes from 300 untreated cases (150 BCC and 150 SCC) and 300 controls to perform these assays. The specific aims of this proposal are: (1) to examine the association between DNA repair capacity and the development of skin carcinomas, (2) to examine the association between mutagen sensitivity and athe development of skin carcinomas, and (3). To examine the association between the frequency of break sites on chromosomes and the development and progression of skin carcinomas, and (4) to evaluate the association of DNA repair capacity with mutagen sensitivity, frequency of chromosomal break sites, gene mutations, and epidemiologic and clinical variables such as sunlight exposure history, clinical stage of disease, and treatment outcomes. We will investigate the relationship between these two genetic susceptibility markers and the development of skin carcinomas in relation to phenotypic characters, family history, sunlight and other carcinogenic exposures, the frequency of mutations in ras oncogenes and p53 tumor suppressor genes clinical stage and progression of tumors (to be collected by Core B; Drs. Margaret Spitz, Randal Weber, and Honnavara Ananthaswamy) and treatment outcomes (to be measured by Drs. Scott Lippman and Reuben Lotan) from the same subjects. This study will provide information regarding the utility of these markers of genetic susceptibility in identifying individuals at high risk of developing skin carcinomas.