The effect of cigarette smoking on lung cancer evolution

The aim of this paper is to elucidate the risk of lung carcinogenesis from cigarette smoking among current and former smokers. To achieve this goal, we have set up a stochastic three-stage model to fit the data of Surveillance, Epidemiology, and End Results (SEER) program besides the data set of smoking derived from the Nurses' Health Study cohort of females (NHS) and the Health Professionals Follow up Study cohort of men (HPFS). The calculations are performed by considering both mutation and clonal expansion rates as parameters in each compartment. For current smokers, our findings show that cigarette smoking has more significant impact on the mutation rates of cells than the clonal expansion rates of premalignant cells among men and women. In particular, for male patients, cigarette smoking affects the mutation in normal cells and the transformation from premalignant cells to malignant ones in the optimal model. In addition, cigarette smoking induces only the initial mutation rates in normal cells among American women. For current and former smokers, cigarette smoking stimulates only the clonal expansion rate of the first premalignant cells in both sexes. However, we find that the impact of cigarette smoking is minimal in former smokers who have stopped smoking for over ten years among men and women in US.