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）。 东道主的作用 对UVR致癌作用的敏感性在两个方面都没有很好的定义， 分子或细胞遗传学水平。 我们建议进行病例对照 评估紫外线辐射的遗传易感性与 （定义为DNA修复能力降低或诱变剂敏感性增加） 以及皮肤癌的发生和发展。 DNA修复 容量将通过宿主细胞再活化试验用UV- 辐照质粒。 将通过UVR诱导的诱变剂敏感性进行测量 染色体断裂和染色体上断裂位点的频率。 我们 将使用来自300例未治疗病例的外周血淋巴细胞（150例BCC和150例BCC-BCC-BCC-BCC-BCC-BCC-BCC-BCC-BCC-BCC-BCC-BCC-BCC-BCC-BCC-BCC-BCC-BCC-BCC-BCC-BCC-BCC-BCC-BCC-BCC-BCC-BCC-BCC-BCC-BCC-BCC-BCC-BCC-BCC-BCC-BCC-BCC-BCC-BCC-BCC-BCC-BCC-BCC-BCC-BCC-BCC-BCC-BCC-BCC-BCC-BCC-BCC-BCC-BCC-BCC-BCC-BCC-BCC-BCC-BCC-BCC-BCC-BCC-BCC-BCC-BCC-BCC-BCC-BCC-BCC-BCC-BCC-BCC-BCC-BCC 150 SCC）和300对照进行这些测定。 的具体目标 这一建议是：（1）检查DNA修复之间的关联 能力和皮肤癌的发展，（2）检查 诱变剂敏感性与皮肤发育异常的关系 癌;（3）. 为了研究在这些疾病中， 染色体上的断裂位点与皮肤的发育和进展 癌，和（4）评估DNA修复能力与 诱变剂敏感性，染色体断裂位点的频率，基因突变， 以及流行病学和临床变量，如阳光照射 病史、疾病的临床分期和治疗结果。 我们将 研究这两种遗传易感性之间的关系 标记物和皮肤癌的发展与表型 性格，家族史，阳光和其他致癌物质的暴露， ras癌基因和p53抑癌基因突变频率 肿瘤的临床分期和进展（由Core B收集; Drs. Margaret Spitz、Randal Weber和Honnavara Ananthaswamy）和治疗 结果（由Scott Lippman和Reuben Lotan博士测量） 同样的主题。 这项研究将提供有关实用程序的信息， 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.