EXPOSURE SPECIFIC MUTATION IN CRITICAL TARGET GENES

关键目标基因的暴露特异性突变

• 批准号: 6432336
• 负责人: JACK A TAYLOR
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6432336
• 关键词: biopsy; bladder neoplasm; bronchoscopy; cancer risk; chemical carcinogen; chemical carcinogenesis; clinical research; cyclophosphamide; dosage; environment related neoplasm /cancer; family genetics; gene environment interaction; gene mutation; human subject; industry; lung neoplasms; minings; molecular oncology; neoplasm /cancer genetics; occupational hazard; oncogenes; polymerase chain reaction; tobacco abuse; tumor suppressor genes; biopsy; bladder neoplasm; bronchoscopy; cancer risk; chemical carcinogen; chemical carcinogenesis; clinical research; cyclophosphamide; dosage; environment related neoplasm /cancer; family genetics; gene environment interaction; gene mutation; human subject; industry; lung neoplasms; minings; molecular oncology; neoplasm /cancer genetics; occupational hazard; oncogenes; polymerase chain reaction; tobacco abuse; tumor suppressor genes

Summary of Work: Carcinoma of the lung, bladder, liver, and pancreas cancers have strong associations with environmental exposures, making them appropriate tumors in which to test the hypothesis that different environmental exposures cause different patterns of mutations in genes that initiate carcinogenesis. Laboratory analysis for two studies have recently been completed in the Molecular and Genetic Epidemiology Section (MAGES) in LMC: Dr. Stern has completed a study of p53 mutation in 64 aflatoxin-associated hepatocellular carcinomas from the Peoples Republic of China and Dr. Slebos has completed a study of K-ras mutation in pancreatic cancers where we have extensive exposure data on DDT, DDE and lifestyle risk factors. Both studies utilized laser capture microdissection to provide enriched tumor cell populations for study. Data analysis is still underway for both studies, although aspects of both studies were presented as posters at AACR. We are currently completing a manuscript on Polb mutation and alternative splicing in bladder tumors. Under a support contract with UNC we are just completing p53 mutational analysis for 200 bladder cancer cases for which we have detailed occupational exposure and extensive genotyping data. Microdissection of these tumors is providing purified tumor cell samples for the next task in this support contract: characterizing the tumors for chromosomal instability using LOH. In collaboration with Dr. Packenham and Ms Devereux we are completing a manuscript on comparative genomic hybridization analysis of selected bladder tumors from arylamine-exposed individuals. A new field study is in the final stages of development and will soon be ready for pilot field work. Fluorescence bronchoscopy and molecular characterization of abnormal bronchial lesions: novel approaches for early detection of lung cancer in high-risk patients obtains preneoplastic lesions in the endobronchial tree from people at high risk of developing lung cancer. Molecular alterations will be determined in these lesions and related to exposure history and probability of progression to higher grade lesions and frank carcinoma. - molecular epidemiology, mutation,carcinogenesis, bladder cancer, lung cancer, tumor suppressor gene, oncogene - Human Subjects

工作摘要：肺，膀胱，肝脏和胰腺癌的癌与环境暴露有着密切的关联，使它们具有适当的肿瘤，以检验以下假说，即不同的环境暴露会导致启动癌变的基因中不同的突变模式。 Laboratory analysis for two studies have recently been completed in the Molecular and Genetic Epidemiology Section (MAGES) in LMC: Dr. Stern has completed a study of p53 mutation in 64 aflatoxin-associated hepatocellular carcinomas from the Peoples Republic of China and Dr. Slebos has completed a study of K-ras mutation in pancreatic cancers where we have extensive exposure data on DDT, DDE和生活方式风险因素。两项研究都利用激光捕获显微解剖来提供富集的肿瘤细胞群进行研究。两项研究仍在进行数据分析，尽管两项研究的各个方面均作为AACR的海报。我们目前正在完成有关PO​​LB突变和膀胱肿瘤中替代剪接的手稿。根据与UNC的支持合同，我们只是完成了200例膀胱癌病例的P53突变分析，我们为此详细介绍了职业暴露和广泛的基因分型数据。这些肿瘤的显微减退为本支持合同中的下一个任务提供了纯化的肿瘤细胞样品：表征使用LOH染色体不稳定性的肿瘤。与Packenham博士和Devereux博士合作，我们正在完成一份关于芳基胺暴露个体的选定膀胱肿瘤比较基因组杂交分析的手稿。一项新的现场研究是在开发的最后阶段，很快就会为试点现场工作做好准备。荧光支气管镜检查和异常支气管病变的分子表征：高危患者的肺癌早期检测的新方法可从患有肺癌患高风险的人的支撑树中获得肿瘤性病变。分子改变将在这些病变中确定，并且与暴露历史以及向高级病变和弗兰克癌的进展有关。 - 分子流行病学，突变，致癌，膀胱癌，肺癌，肿瘤抑制基因，癌基因 - 人类受试者