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

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

工作总结：肺癌、膀胱癌、肝癌和胰腺癌与环境暴露有很强的相关性，使它们成为合适的肿瘤，以检验不同的环境暴露导致启动致癌作用的基因突变的不同模式的假设。LMC的分子和遗传流行病学部门最近完成了两项研究的实验室分析：Stern博士完成了一项关于中国64例黄曲霉毒素相关肝细胞癌中p53突变的研究，Slebos博士完成了一项关于胰腺癌中K-ras突变的研究，我们有大量关于DDT，DDE和生活方式风险因素的暴露数据。两项研究均采用激光捕获显微切割技术，为研究提供富集的肿瘤细胞群。这两项研究的数据分析仍在进行中，尽管这两项研究的各个方面都在AACR上作为海报展示。我们目前正在完成一份关于膀胱肿瘤中Polb突变和选择性剪接的手稿。根据与CNAS的支持合同，我们刚刚完成了200例膀胱癌病例的p53突变分析，我们有详细的职业暴露和广泛的基因分型数据。这些肿瘤的显微解剖为该支持合同的下一项任务提供了纯化的肿瘤细胞样本：使用洛来表征肿瘤的染色体不稳定性。在与Packenham博士和Devereux女士的合作中，我们正在完成一份关于对来自芳胺暴露个体的选定膀胱肿瘤进行比较基因组杂交分析的手稿。一项新的实地研究正处于最后拟订阶段，不久将准备进行试点实地工作。荧光支气管镜检查和异常支气管病变的分子特征：早期检测高危患者肺癌的新方法从肺癌高危人群中获得支气管内树的癌前病变。将在这些病变中确定分子改变，并与暴露史和进展为更高级别病变和坦率癌的概率相关。- 分子流行病学，突变，致癌作用，膀胱癌，肺癌，肿瘤抑制基因，癌基因-人类受试者