Abstract
BACKGROUND: Smoking is a pivotal modifiable risk factor for lung cancer (LC). Previous studies have indicated that a smoking cessation program might be incorporated into the LC screening program. However, the effects of smoking cessation and its duration with the age at onset (AAO) of LC, all-cause mortality, and LC-specific mortality remain unclear. We aimed to comprehensively investigate the association of smoking cessation-related behaviors on the AAO of LC, LC-specific and all-cause mortality. METHODS: A total of 2671 smokers with LC as the primary site from the UK Biobank were included in this study, with a 7:3 ratio assigned randomly to a discovery set (n = 1872) and a validation set (n = 799). Generalized linear regression models were used for AAO of LC outcomes and Cox models for mortality outcomes. RESULTS: Participants over 60 years old could still benefit from smoking cessation to prolong AAOs (β = 1.613 for men, P = 0.003; β = 1.533 for women, P = 0.018). A cessation duration of > 15 years was associated with a later AAO in men (P < 0.001). Moreover, smoking cessation before 60 years old, especially among those under 40 years, was significantly associated with a lower risk of all-cause mortality (men: hazard ratio (HR): 0.65 [95% confidence interval 0.51-0.83]; women: 0.62 [0.47-0.83]) and LC-specific mortality (men: 0.67 [0.51-0.87]; women: 0.68 [0.50-0.92]). Compared with continuous smokers, former smokers who quit smoking for more than 15 years had a lower risk of all-cause mortality (men: 0.70 [0.59-0.84]; women: 0.68 [0.56-0.84]) and LC-specific mortality (men: 0.71 [0.59-0.87]; women: 0.69 [0.56-0.86]). CONCLUSIONS: Smoking cessation after 60 years old may still be helpful for a later AAO of LC. Former smokers who quit smoking for more than 15 years have a reduced risk of developing LC and mortality.