Lung Cancer in the US: Pathogenesis, Trends, Prevention

描述（由申请人提供）使用SEER数据库，该数据库覆盖了超过10%的美国人口，将使用年龄-队列-时期模型的扩展研究1973-1998年期间的肺癌发病率趋势。 具体而言，它建议开发模型，其中非特定的年龄效应被替换为参数风险函数，承认多阶段性质的致癌作用。 至少在形式上，这一过程巧妙的任意线性趋势，困扰传统的年龄队列时期模型的众所周知的问题。 此外，使用基于生物学的模型对SEER等大型登记研究中仔细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的潜在机制。 关于时间趋势，将尝试将美国肺癌发病率趋势与吸烟习惯趋势联系起来。 烟草烟雾含有诱变剂和影响细胞增殖动力学的试剂。 因此，烟草烟雾在肺癌发生中可能既是启动剂又是促进剂。 这些分析的一个目标是调查非特异性和出生队列和日历年的趋势是否可以直接与癌症发生的特定方面，如启动，促进和进展。 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数据库的规模较大，因此应该可以按人种、性别和组织学类型分别进行这些分析。最后，最佳多阶段模型的估计参数将被用来预测肺癌发病率的趋势，在各种假设下的香烟和吸烟习惯的组成的变化。

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.