Smoking Cessation and Risk of Esophageal Cancer by Histological Type: Systematic Review and Meta-analysis

Background: Tobacco smoking strongly increases risk of esophageal squamous cell carcinoma and moderately increases risk of esophageal adenocarcinoma. How smoking cessation influences esophageal cancer risk across histological subtypes, time latencies, and geographic regions is not clear. Methods: Studies were systematically searched on Medline, Embase, Web of Science, Cochrane Library, and ClinicalTrials.gov. Pooled estimates of risk ratios (RRs) were derived using a random effects model. Cochran's Q test and I2 statistic were used to detect heterogeneity. Results: Among 15 009 studies, 52 fulfilled the inclusion criteria. Using nonsmokers as a reference, risk of esophageal squamous cell carcinoma was lower among former smokers (RR = 2.05, 95% confidence interval [CI] = 1.71 to 2.45) than among current smokers (RR = 4.18, 95% CI = 3.42 to 5.12). Compared with current smokers, a strong risk reduction was evident after five or more years (RR = 0.59, 95% CI = 0.47 to 0.75), and became stronger after 10 or more years (RR = 0.42, 95% CI = 0.34 to 0.51) and 20 or more years (RR = 0.34, 95% CI = 0.25 to 0.47) following smoking cessation. The risk reduction was strong in Western populations, while weak in Asian populations. Using nonsmokers as reference, the risk of esophageal adenocarcinoma was only slightly lower among former smokers (RR = 1.66, 95% CI = 1.48 to 1.85) than among current smokers (RR = 2.34, 95% CI = 2.04 to 2.69). The risk of esophageal adenocarcinoma did not show any clear reduction over time after smoking cessation, with a risk ratio of 0.72 (95% CI = 0.52 to 1.01) 20 or more years after smoking cessation, compared with current smokers. Conclusions: Smoking cessation time-dependently decreases risk of esophageal squamous cell carcinoma, particularly in Western populations, while it has limited influence on the risk of esophageal adenocarcinoma.