Lung Cancer in the US: Pathogenesis, Trends, Prevention

使用覆盖超过10%美国人口的SEER数据库，将使用年龄队列模型的扩展来调查1973-1998年期间肺癌发病率趋势。具体而言，建议开发模型，其中非特异性年龄效应被参数危害函数所取代，该函数承认癌变的多阶段性质。至少在形式上，这一过程解决了困扰传统年龄群模型的任意线性趋势的众所周知的问题。此外，使用基于生物学的模型对大型登记处（如SEER）精心收集的发病率数据进行分析，除了揭示时间趋势外，还可以深入了解致癌机制。关于时间趋势，将尝试将肺癌发病率的趋势与美国吸烟习惯的趋势联系起来。烟草烟雾中含有诱变剂和影响细胞增殖动力学的物质。因此，烟草烟雾在肺癌发生过程中可能既是引发者又是促进者。这些分析的目标之一是调查非特异性、出生队列和历年趋势是否与癌变的特定方面（如开始、促进和进展）直接相关。将通过将烟草消费趋势纳入多阶段模型的参数来研究这种可能性。由于SEER数据库的规模很大，应该可以根据种族、性别和组织学类型分别进行这些分析。最后，最优多阶段模型的估计参数将用于在有关香烟成分和吸烟习惯变化的各种假设下预测未来肺癌发病率趋势。

DESCRIPTION (provided by applicant)Using the SEER database, which covers more than 10% of the US population, lung cancer incidence trends over the period 1973-1998 will be investigated using extensions of age-cohort-period models. Specifically, it is proposed to develop models in which non-specific age effects are replaced by parametric hazard functions that acknowledge the multistage nature of carcinogenesis. At least formally, this procedure finesses the well known problem of arbitrary linear trends that plagues the traditional age-cohort-period models. Furthermore, analyses of carefully collected incidence data in large registries such as SEER using biologically-based modelscan lead to insights in to the mechanisms underlying carcinogenesis in addition to shedding light on temporal trends. With respect to temporal trends, attempts will be made to relate trends in lung cancer incidence to trends in smoking habits in the US. Tobacco smoke contains both mutagens and agents that impact cell proliferation kinetics. Thus, tobacco smoke probably acts as both an initiator and a promoter in lung carcinogenesis. One goal of these analyses is to investigate whether non-specific and birth cohort and calendar year trends can be directly linked to specific aspects of carcinogenesis, such as initiation, promotion and progression. This possibility will be investigated by incorporating tobacco consumption trends into the parameters of the multistage model. Because of the large size of the SEER database it should be possible to conduct these analyses separately by race, sex and histologic type. Finally, the estimated parameters of the optimal multistage model will be used to project lung cancer incidence trends into the future under various assumptions regarding changes in composition of cigarettes and smoking habits.