Lung Cancer in the US: Pathogenesis, Trends, Prevention

描述(申请人提供)利用覆盖超过10%的美国人口的SEER数据库，将使用年龄队列时期模型的扩展来调查1973-1998年期间的肺癌发病率趋势。具体地说，有人建议开发模型，在该模型中，非特定年龄效应被承认癌症发生的多阶段性质的参数风险函数所取代。至少在形式上，这个过程巧妙地解决了困扰传统年龄队列时期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SEER等大型登记中仔细收集的发病率数据进行分析，除了揭示时间趋势外，还可以深入了解癌症发生的潜在机制。在时间趋势方面，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。烟草烟雾既含有诱变剂，又含有影响细胞增殖动力学的物质。因此，烟草烟雾可能既是肺癌发生的始发者，也是肺癌发生的促进者。这些分析的一个目标是调查非特定的出生队列和历年趋势是否可以直接与癌症发生的特定方面联系在一起，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调查这种可能性。由于SEER数据库的规模很大，应该可以按种族、性别和组织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被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.