ANALYSIS OF LUNG CANCER MORTALITY RECORDS/DEVELOP QUANTITATIVE WORKING MODEL

分析肺癌死亡率记录/开发定量工作模型

• 批准号: 6106416
• 负责人: William G Thilly
• 金额: $ 22.21万
• 依托单位: MASSACHUSETTS INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-08-01 至 2000-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6106416
• 关键词: age difference; air pollution; carcinogenesis; clinical research; cocarcinogen; environment related neoplasm /cancer; gene mutation; genetic models; human data; human mortality; human population genetics; mathematical model; model design /development; neoplasm /cancer epidemiology; neoplasm /cancer genetics; neoplastic transformation; preneoplastic state; respiratory disorder epidemiology; respiratory epithelium; rural area; smoking; tobacco abuse; urban area

We have collected the data for all forms of mortality reported to the U.S. Public Health Service from 1900 to the present day and carefully matched these records to the sizes of the populations form which the reports were made. With these data we are able to observe the age-specific mortality rates for birth cohorts reaching to the early nineteenth century. With these data we have undertaken development of quantitative working model of lung cancer building on the general models of Knudson and Moolgavkar. This model uses what is known about the number and kind of genetic changes which occur early in carcinogenesis and age-specific mutant fractions in human somatic cells to derive estimates of the rate for key processes in cancer initiation and progression in lung epithelium of smokers and non- smokers. In particular we have been able to make quantitative predictions for the rates of initiation mutations, the growth rates in intermediate pre-neoplastic colonies and the rates of mutation in such colonies leading to a frankly neoplastic cell. Our model does not extend to the mutations and population dynamics of adenocarcinomas or carcinomas, as these, which occur in a relatively short time, cannot be derived from age-specific mortality data. These quantitative predictions serve as quantitative hypothesis about the effects of exposure to tobacco smoke and urban pollutants on mutation rates and cell kinetics in human lungs. Because the national mortality data do not allow us to address the possible effect of urban air exposure and lifetime lung cancer probabilities, we have begun analysis of the mortality in all cities, towns and villages in Massachusetts using the computerized records from 1969 to the present data. Classifying reporting units as rural, suburban or urban we will re-examine the general contention that urban residents have a higher age-specific lung cancer rate with attention to the age- specific lung cancer rate parameters that night differ as a function of residential location. This analysis may allow us to identify any interaction between urban/rural residence and cigarette smoking, since the great preponderance of lung cancer cases are among smokers.

我们已经收集了向美国报告的所有形式死亡率的数据 从1900年到今天的公共卫生服务，并精心匹配 这些记录到报告的大小的大小 制成。使用这些数据，我们能够观察到特定年龄的死亡率 到19世纪初的出生人群率。 通过这些数据，我们已经开发了定量工作 Knudson和Knudson和 Moolgavkar。 该模型使用有关遗传变化的数量和类型的知识 这是在癌变和年龄特异性突变分数中发生的 人类体细胞以得出对关键过程率的估计 吸烟者肺上皮的癌症开始和进展 吸烟者。特别是我们能够做出定量预测 对于起始突变的速率，中级的增长率 这些菌落中的肿瘤前菌落和突变率 坦率地讲述肿瘤细胞。我们的模型不会扩展到突变 以及腺癌或癌的种群动态，如这些 发生在相对较短的时间内，不能源自特定年龄 死亡率数据。 这些定量预测是关于 暴露于烟草烟雾和城市污染物对突变的影响 人肺的率和细胞动力学。 因为国家死亡率数据不允许我们解决 城市空气暴露和终生肺癌的可能影响 概率，我们已经开始对所有城市的死亡率进行分析， 马萨诸塞州的城镇和村庄使用计算机化记录 1969年到当前数据。将报告单位分类为农村，郊区 或城市，我们将重新审视城市居民的一般论点 具有更高年龄特异性的肺癌率，注意年龄 夜晚的特定肺癌率参数随着 住宅地点。这种分析可能使我们能够确定任何 城市/农村住宅与吸烟之间的相互作用，因为 吸烟者中有很大的肺癌病例。