MULTIPLE PRIMARY CANCERS AND MUTAGEN HYPERSENSITIVITY

多种原发性癌症和诱变剂过敏

• 批准号: 3201488
• 负责人: Stimson P Schantz
• 金额: $ 5.84万
• 依托单位: SLOAN-KETTERING INST CAN RESEARCH
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-09-01 至 1995-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3201488
• 关键词: alcoholic beverage consumption; bleomycin; blood chemistry; cancer prevention; cancer risk; case history; chemical carcinogen; chemical carcinogenesis; chromosome aberrations; cytogenetics; environment related neoplasm /cancer; environmental toxicology; head /neck neoplasm; human subject; interview; longitudinal human study; metastasis; multiple primary neoplasia; neoplasm /cancer epidemiology; neoplasm /cancer genetics; physical chemical interaction; questionnaires; statistics /biometry; tobacco abuse

The development of head and neck cancer may depend upon an interaction both environmental carcinogens and a genetic susceptibility to those carcinogens. The need to understand such interaction in the head and neck cancer population is heightened by their associated risk for the development of second primary neoplasias, such as lung and digestive tract cancers. With an improved understanding, the relative risk of second malignancies can be more precisely defined. Preventive therapy could then be more appropriately targeted. The head and neck cancer population thus represents a potential target population for prevention of multiple diverse environmentally-induced cancers. It will, therefore be demonstrated by this proposal, that head and neck cancer patients express chromosomal susceptibility to mutagens. Specifically, cultured lymphocytes will be exposed to the clastogen bleomycin, arrested in metaphase, and assessed for bleomycin-induced chromatid breaks in cytogenetic preparations. Results gathered from the head and neck cancer population will be compared to age- and sex-matched non-cancer afflicted controls. Using case-control epidemiologic methodology, chromosome sensitivity will be evaluated as a risk factor for head and neck cancer development. Finally, the relationship of total carcinogen exposure (namely, to tobacco and alcohol) both before and after treatment to probability of second malignancy development will be identified through the formulation of a quantitative risk assessment model. The impact of adding quantitative measures of a respective patient's mutagen-hypersensitivity, as determined by the bleomycin assay, to the quantitative risk assessment model will be demonstrated. Results from this study will form a basis for determining the potential biologic significance of chromosomal sensitivity in cancer development. Results will, likewise provide insight into future stratification considerations for therapeutic intervention trials involving prevention of second malignancies in the head and neck cancer population.

头颈癌的发展可能取决于相互作用 环境致癌物和对那些的遗传敏感性 致癌物。 需要了解头部和颈部的这种互动 癌症人群的相关风险增加了 开发第二个主要的肿瘤，例如肺和消化道 癌症。 有了改善的理解，第二个相对风险 恶性肿瘤可以更精确地定义。 然后可以预防治疗 更适合目标。 头部和颈部癌的种群 代表了预防多元化的潜在目标人群 环境引起的癌症。 因此，它将证明 该提议，头颈癌患者表达染色体 对诱变剂的敏感性。 具体而言，培养的淋巴细胞将是 暴露于Clastogen博来霉素，在中期被捕并评估 博来霉素诱导的细胞遗传学制剂中的染色单体断裂。 结果 从头部和颈部癌的种群中收集到的年龄将进行比较 和性别匹配的非癌症对照。 使用病例对照 流行病学方法论，染色体敏感性将被评估为 头颈癌发展的危险因素。 最后， 总致癌物暴露的关系（即烟草和酒精） 治疗前后，第二次恶性肿瘤的概率 将通过制定定量来确定发展 风险评估模型。 添加A的定量度量的影响 各自患者的诱变 - 亚果皮，由 博来霉素分析，定量风险评估模型将是 证明。 这项研究的结果将构成确定的基础 染色体敏感性在癌症中的潜在生物学意义 发展。 结果同样将提供对未来的见解 涉及治疗干预试验的分层注意事项 预防头颈癌种群中的第二次恶性肿瘤。