EXPOSURE SPECIFIC MUTATION IN CRITICAL TARGET GENES

关键目标基因的暴露特异性突变

• 批准号: 6106695
• 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/6106695
• 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: Lung and bladder 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 gene that initiate carcinogenesis. We have designed a series of studies to test this hypothesis. For lung cancer this includes studies of uranium miners in Colorado and Czechoslovakia; nickel smelter workers, asbestos-exposed workers, and vinyl chloride- exposed workers in Norway; and smokers and non-smokers from the U.S. For bladder cancer it includes studies of arylamine-exposed workers in Georgia and of DuPont workers in New Jersey, cyclophosphamide-treated patients from Denmark, and smokers and non-smokers from the U.S. We have published a series of papers on ras, p53, and p15 and p16 mutations and LOH from these studies. Efforts in the past year have been directed at developing new clinical collaborations and the laboratory development of comparative genomic hybridization (CGH) from fixed tissue. With the Pulmonary Medicine Clinic at University of North Carolina we are developing a study of the molecular events in early preneoplastic lesions utilizing fluorescent bronchoscopy. Fluorescent bronchoscopy allows detection of dysplastic lesions not visible using regular light bronchoscopy, and such lesions can be biopsied and followed over time. In addition we are developing a collaboration with the Mayo Clinic to provide lung tumor samples from interesting subgroups: non-smokers, and patients with first degree relatives with lung cancers as well as population-based samples. On the laboratory side, Dr. Packenham has been working with selected fixed bladder cancer samples to develop degenerative oligonucleotide priming (DOP) PCR to allow us to do CGH on fixed tissue specimens.

工作总结：肺癌和膀胱癌 与环境暴露密切相关，使它们 适当的肿瘤来检验不同的假设 环境暴露导致不同模式的突变 引发癌变的基因。我们设计了一系列 研究来检验这一假设。对于肺癌，这包括研究 科罗拉多州和捷克斯洛伐克的铀矿矿工；镍冶炼厂 工人、接触石棉的工人和接触氯乙烯的工人 挪威的工人；以及来自美国的吸烟者和非吸烟者 对于膀胱癌，它包括对接触芳基胺的工人的研究 佐治亚州和新泽西州的杜邦工人， 来自丹麦的接受环磷酰胺治疗的患者和吸烟者 和来自美国的非吸烟者。我们发布了一系列 有关 ras、p53、p15 和 p16 突变以及 LOH 的论文 这些研究。过去一年的努力方向 发展新的临床合作和实验室 比较基因组杂交（CGH）的发展 固定组织。与大学肺科诊所合作 北卡罗来纳州我们正在开展一项分子事件研究 利用荧光支气管镜检查早期肿瘤前病变。 荧光支气管镜检查可以检测发育异常病变，但不能 使用常规光支气管镜检查可以看到此类病变 进行活检并随时间推移进行随访。此外，我们正在开发一个 与梅奥诊所合作提供肺部肿瘤样本 来自有趣的亚组：非吸烟者和首次吸烟的患者 患有肺癌的亲属以及基于人口的 样品。在实验室方面，Packenham 博士一直致力于 使用选定的固定膀胱癌样本来开发退行性 寡核苷酸引发 (DOP) PCR 使我们能够进行 CGH 固定组织标本。