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.

我们收集了报告给美国的所有形式的死亡率数据