ANALYSIS OF LUNG CANCER MORTALITY RECORDS/DEVELOP QUANTITATIVE WORKING MODEL

我们收集了报告给美国的所有形式的死亡率数据。 从1900年到今天的公共卫生服务并精心匹配 这些记录的人口规模的形式，报告 进行了通过这些数据，我们可以观察到特定年龄的死亡率 到世纪初的出生人口比率。 利用这些数据，我们进行了定量工作的开发 在Knudson模型和 穆尔加夫卡 这个模型使用了已知的基因变化的数量和种类 发生在癌变的早期， 人类体细胞，以获得关键过程的速率估计， 吸烟者和非吸烟者的肺上皮中的癌症发生和进展 吸烟者。特别是我们已经能够作出定量预测 对于起始突变率，中间体的生长率 肿瘤前集落和这些集落中的突变率导致 一个肿瘤细胞。我们的模型没有扩展到突变 和腺癌或癌的群体动态，如这些， 在相对较短的时间内发生，不能从年龄特异性 死亡率数据。 这些定量的预测作为定量的假设， 暴露于烟草烟雾和城市污染物对突变的影响 率和细胞动力学。 因为国家死亡率数据不允许我们解决 城市空气暴露与终生肺癌的可能影响 概率，我们已经开始分析所有城市的死亡率， 马萨诸塞州的城镇和村庄使用计算机记录， 从1969年到现在的数据。将报告单位分类为农村、郊区 我们将重新审视城市居民 有更高的年龄特异性肺癌发病率， 夜间不同的特定肺癌率参数是 住宅位置。这一分析可以帮助我们确定任何 城市/农村居民与吸烟之间的相互作用， 吸烟者是肺癌的主要高发人群。

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.