RESPIRATORY CARCINOGENESIS IN URANIUM MINERS

这项申请提出了一个关于肺癌的综合工作计划 基于前者的高风险提供的研究机会 新墨西哥州和科罗拉多州的铀矿工对这种恶性疾病负责。该计划 包括调查与以下因素有关的肺癌数量风险 氡子体暴露、敏感度决定因素和 致癌的分子和细胞标记物。对研究的需要 这些领域是显而易见的。肺癌仍然是一个紧迫的全球公众问题 健康问题和室内氡现在被认为是第二大主导因素 在美国是肺癌的起因。分子生物学和分子生物学技术 细胞生物学提供了新的标志物来描述纵向 致癌过程和筛查。 铀矿工患肺癌的额外风险显著增加 是由氡子体暴露和吸烟决定的。《纽约时报》 墨西哥、科罗拉多州、亚利桑那州和犹他州有大量的前矿工 因为这些暴露，他们现在患肺癌的风险很高。我们 已经在3500人的队列中调查了肺癌的风险 新墨西哥州铀矿矿工和纳瓦霍铀矿矿工。该计划 在本申请中描述的将这些研究扩展到以下分子 流行病学模型。它利用了《纽约时报》的流行病学资源 癌症研究和治疗中心的墨西哥肿瘤登记处 美国新墨西哥大学分子和细胞生物学专业 洛夫莱斯吸入毒理研究所。申请者将会 作为跨学科研究团队的成员参与 实施关于肺癌分子流行病学的广泛计划 在铀矿工身上。在这个奖项的三年时间里，他将使用 来自该项目的初始数据和来自其他资源的铀数据 矿工们要完成以下工作： L。使用一组新开发的高风险铀矿工， A)确定蜂窝和 呼吸道脱落细胞的分子变化和 确定它们与氡暴露和吸烟的关系； 和 B)描述细胞和分子的时间模式 呼吸道癌变的事件与队列 纵向紧随其后；以及 C)量化与细胞癌有关的肺癌风险 以及流行程度较高的分子标记。 2.使用新墨西哥州肿瘤登记数据库#年发生的癌症 纳瓦霍族男性，1969-1993年。 A)确定铀--的数量和时间趋势 与肺癌相关的采矿风险； B)描述纳瓦霍语组织类型的分布 男性和一群新墨西哥州的铀矿工人； 3.使用在全州范围内进行筛选的地下矿工队列 由矿工科尔法克斯医疗中心实施的筛查计划， A)评估肺功能作为肺癌的标志 易感性；以及 B)确定与存在相关的肺癌风险 死于矽肺病。

This application proposes an integrated program of work on lung cancer based on the research opportunity afforded by the high risk of former uranium miners in New Mexico and Colorado for this malignancy. The program includes investigation of quantitative risks of lung cancer in relation to exposure to radon progeny, of determinants of susceptibility, and of molecular and cellular markers of carcinogenesis. The need for research in these areas is evident. Lung cancer remains a pressing worldwide public health problem and indoor radon is now recognized as the second leading cause of lung cancer in the United States. Techniques of molecular and cellular biology provide new markers for describing the longitudinal process of carcinogenesis and for screening. Uranium miners have a markedly increased excess risk of lung cancer that is determined by exposure to radon progeny and smoking. The states of New Mexico, Colorado, Arizona, and Utah have a large number of former miners who are now at high risk for lung cancer because of these exposures. We have already investigated the risks of lung cancer in a cohort of 3,500 New Mexico uranium miners and in Navajo uranium miners. The program described in this application extends these studies following a molecular epidemiology model. It draws on resources in epidemiology at the New Mexico Tumor Registry in the Cancer Research and Treatment Center at the University of New Mexico and in molecular and cellular biology at the Lovelace Inhalation Toxicology Research Institute. The applicant will participate as a member of the interdisciplinary research team that is implementing a broad program on the molecular epidemiology of lung cancer in uranium miners. During the three years of this award, he will use the initial data from the project and data from other resources on uranium miners to accomplish the following: l. Using a newly developed cohort of high risk uranium miners, a) determine the prevalence on enrollment of cellular and molecular changes in exfoliated respiratory cells and define their relationship to radon exposure and smoking; and b) describe the temporal pattern of cellular and molecular events in respiratory carcinogenesis as the cohort is followed longitudinally; and c) Quantify the lung cancer risk associated with cellular and molecular markers that occur with high prevalence. 2. Using the New Mexico Tumor Registry database on incident cancers in Navajo males, 1969-1993. a) determine the magnitude and temporal trends in uranium- mining associated risk of lung cancer; b) describe the distribution of histologic types in Navajo males and a cohort of New Mexico uranium miners; 3. Using the cohort of underground miners screened through a state wide screening program operated by the Miners' Colfax Medical Center, a) assess pulmonary function as a marker of lung cancer susceptibility; and b) determine lung cancer risk associated with the presence of silicosis.