Multistage carcinogenesis and lung cancer mortality in three cohorts
Multistage carcinogenesis and lung cancer mortality in three cohorts
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DOI：
10.1158/1055-9965.epi-04-0756
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发表时间：
2005-05-01
影响因子：
3.8
通讯作者：
Moolgavkar, SH
中科院分区：
文献类型：
--
作者：
Hazelton, WD;Clements, MS;Moolgavkar, SH
实验证据表明，烟草烟雾在肺癌发生过程中既起引发剂作用，又起促进剂作用。我们使用两阶段克隆扩增模型，结合启动，促进和恶性转化的想法，分析三个大型队列（英国医生队列和两个美国癌症协会队列）的肺癌死亡率，以确定吸烟习惯如何通过这些机制影响年龄特异性肺癌发病率。似然比检验表明，在所有队列中，吸烟相关促进是与肺癌死亡率相关的主要模型机制。吸烟相关的启动是不太重要的推广，但相互作用协同it.Although在这些数据中没有关于戒烟者的信息，模型估计变量可以用来预测戒烟者之间的风险。这些预测的风险与其他研究得出的戒烟者的风险非常一致。我们提出了10年的预测风险，目前和以前的吸烟者调整的竞争性死亡原因。在这些人群中，吸烟持续时间对肺癌风险的重要性是推广的直接结果。干预和治疗策略应侧重于促进作为肺癌发生的主要病因机制。
Experimental evidence indicates that tobacco smoke acts both as an initiator and a promoter in lung carcinogenesis. We used the two-stage clonal expansion model incorporating the ideas of initiation, promotion, and malignant conversion to analyze lung cancer mortality in three large cohorts, the British Doctors' cohort and the two American Cancer Society cohorts, to determine how smoking habits influence age-specific lung cancer rates via these mechanisms. Likelihood ratio tests indicate that smoking-related promotion is the dominant model mechanism associated with lung cancer mortality in all cohorts. Smoking-related initiation is less important than promotion but interacts synergistically with it. Although no information on ex-smokers is available in these data, the model with estimated variables can be used to project risks among ex-smokers. These projected risks are in good agreement with the risk among ex-smokers derived from other studies. We present 10-year projected risks for current and former smokers adjusted for competing causes of mortality. The importance of smoking duration on lung cancer risk in these cohorts is a direct consequence of promotion. Intervention and treatment strategies should focus on promotion as the primary etiologic mechanism in lung carcinogenesis.