Lifetime Smoking History and Risk of Lung Cancer: Results From the Framingham Heart Study

Background: The relative risk of lung cancer decreases with years since quitting (YSQ) smoking, but risk beyond 25 YSQ remains unclear. Current lung cancer screening guidelines, which exclude smokers with more than 15 YSQ, may not detect lung cancers in this population. Methods: We analyzed data from Framingham Heart Study Original (n = 3905) and Offspring cohort (n = 5002) participants for lifetime smoking and lung cancer incidence from 1954 to 1958 (Exam 4) and 1971 to 1975 (Exam 1), respectively, through 2013. We used multivariable-adjusted Cox proportional hazards regression models to compare current, former, and never smokers and lung cancer risk. Smoking status and covariates were time-updated every two years (Original) or four years (Offspring). Primary analyses were restricted to heavy ever smokers with more than 21.3 pack-years; additional analyses included all ever smokers. Results: On follow-up (median = 28.7 years), 284 lung cancers were detected: incidence rates/1000 person-years in current, former, and never smokers were 1.97 (95% confidence interval [CI] = 1.66 to 2.33), 1.61 (95% CI = 1.34 to 1.93), and 0.26 (95% CI = 0.17 to 0.39), respectively. Heavy former (vs never) smokers had elevated lung cancer risk at all YSQ (<5: hazard ratio [HR] = 12.12, 95% CI = 6.94 to 21.17; 5-9: HR = 11.77, 95% CI = 6.78 to 20.45; 10-14: HR = 7.81, 95% CI = 3.98 to 15.33; 15-24: HR = 5.88, 95% CI = 3.19-10.83; ≥25: HR = 3.85, 95% CI = 1.80 to 8.26). Heavy former (vs current) smokers had 39.1% lower lung cancer risk within five YSQ. Among all former smokers, 40.8% of lung cancers occurred after more than 15 YSQ. Conclusions: Among heavy former smokers, lung cancer risk drops within five YSQ relative to continuing smokers, yet it remains more than threefold higher than never smokers after 25 YSQ. Four of ten lung cancers occurred in former smokers with more 15 YSQ, beyond the screening window of the current guideline.