Weight Gain After Smoking Cessation and Cancer Risk in 3 Prospective Cohorts in the United States

BACKGROUND: It remains unknown how cancer risks vary by duration of smoking cessation and whether the benefit is attenuated by postcessation weight gain. METHODS: We prospectively followed 198 565 persons from the Nurses’ Health Study (1978-2016), Nurses’ Health Study II (1991-2017), and Health Professionals Follow-up Study (1988-2016) who were free of cancer at baseline. We used proportional hazard Cox models to compare cancer risk between current smokers and former smokers with different durations of smoking cessation and postcessation weight gains. RESULTS: During 4 718 199 person-years of follow-up, we identified 32 456 cases of total cancer. Compared with current smokers, the risks for total and smoking-related cancer in past smokers were reduced to the level similar to never smokers after abstaining smoking for more than 26 years, with the hazard ratio of 0.69 (95% confidence interval [CI] = 0.63 to 0.76) for total cancer and 0.31 (95% CI = 0.26 to 0.37) for smoking-related cancer, whereas no risk reduction was found for obesity-related cancer. Comparing former smokers with current smokers, the multivariable-adjusted hazard ratios for postcessation weight gain of 0-4.9 kg, 5-9.9 kg, and 10 kg or higher were 0.85 (95% CI = 0.81 to 0.89), 0.88 (95% CI = 0.83 to 0.93), and 0.93 (95% CI = 0.88 to 1.00) for total cancer and 0.62 (95% CI = 0.58 to 0.67), 0.65 (95% CI = 0.60 to 0.71), and 0.71 (95% CI = 0.65 to 0.78) for total smoking-related cancer. In contrast, higher weight gain following smoking cessation was associated with a modest increased obesity-related cancer risk. CONCLUSION: Smoking cessation overall has a strong net association with lower risk of total cancer irrespective of weight gain. However, this inverse association may be attenuated by substantial postcessation weight gain, largely because of an increased risk of obesity-related cancers.