ANALYSIS OF LUNG CANCER MORTALITY RECORDS/DEVELOP QUANTITATIVE WORKING MODEL

我们已经收集了向美国报告的所有形式的死亡数据。 1900年至今的公共卫生服务与精心匹配 这些记录与报告所形成的人口规模有关 制造。有了这些数据，我们就能够观察特定年龄段的死亡率 出生队列的比率达到19世纪初。 利用这些数据，我们进行了量化工作的开展 建立在Knudson和Knudson一般模型基础上的肺癌模型 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 它们发生在癌变的早期和年龄相关的突变部分 人类体细胞推导出关键过程的比率估计 吸烟者和非吸烟者肺上皮细胞癌的发生发展 吸烟者。特别是，我们已经能够做出定量的预测 对于起始突变的速率，中间体的生长速率 肿瘤前集落和这些集落中的突变率 直率地说是肿瘤细胞。我们的模型不适用于突变 和腺癌或癌的种群动态，如这些， 发生在相对较短的时间内，不能从特定的年龄派生 死亡数据。 这些定量预测可以作为关于 烟草烟雾和城市污染物暴露对突变的影响 人体肺部的速率和细胞动力学。 因为全国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来自 从1969年到现在的数据。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普遍论点 有较高的特定年龄肺癌发病率，并注意年龄- 当晚特定的肺癌发病率参数作为以下因素的函数而不同 住宅区。这一分析可能使我们能够识别出 城乡居民与吸烟之间的相互作用，因为 肺癌病例中吸烟者占很大比例。

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.