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Keywords:

  • TSCE model;
  • lung cancer;
  • genetic susceptibility;
  • cigarette smoking

Abstract

Numerous prospective and retrospective studies have clearly demonstrated a dose-related increased lung cancer risk associated with cigarette smoking, with evidence also for a genetic component to risk. In this study, using the two-stage clonal expansion stochastic model framework, for the first time we investigated the roles of both genetic susceptibility and smoking history in the initiation, clonal expansion, and malignant transformation processes in lung carcinogenesis, integrating information collected by a case–control study and a large-scale prospective cohort study. Our results show that individuals with suboptimal DNA repair capacity have enhanced transition rates of key events in carcinogenesis. © 2008 Wiley-Liss, Inc.