Cigarette smoking and adenocarcinomas of the esophagus and esophagogastric junction: a pooled analysis from the international BEACON consortium

Abstract

Background: Previous studies that showed an association between smoking and adenocarcinomas of the esophagus and esophagogastric junction were limited in their ability to assess differences by tumor site, sex, dose-response, and duration of cigarette smoking cessation.

Methods: We used primary data from 10 population-based case-control studies and two cohort studies from the Barrett's Esophagus and Esophageal Adenocarcinoma Consortium. Analyses were restricted to white non-Hispanic men and women. Patients were classified as having esophageal adenocarcinoma (n = 1540), esophagogastric junctional adenocarcinoma (n = 1450), or a combination of both (all adenocarcinoma; n = 2990). Control subjects (n = 9453) were population based. Associations between pack-years of cigarette smoking and risks of adenocarcinomas were assessed, as well as their potential modification by sex and duration of smoking cessation. Study-specific odds ratios (ORs) estimated using multivariable logistic regression models, adjusted for age, sex, body mass index, education, and gastroesophageal reflux, were pooled using a meta-analytic methodology to generate summary odds ratios. All statistical tests were two-sided.

Results: The summary odds ratios demonstrated strong associations between cigarette smoking and esophageal adenocarcinoma (OR = 1.96, 95% confidence interval [CI] = 1.64 to 2.34), esophagogastric junctional adenocarcinoma (OR = 2.18, 95% CI = 1.84 to 2.58), and all adenocarcinoma (OR = 2.08, 95% CI = 1.83 to 2.37). In addition, there was a strong dose-response association between pack-years of cigarette smoking and each outcome (P < .001). Compared with current smokers, longer smoking cessation was associated with a decreased risk of all adenocarcinoma after adjusting for pack-years (<10 years of smoking cessation: OR = 0.82, 95% CI = 0.60 to 1.13; and > or =10 years of smoking cessation: OR = 0.71, 95% CI = 0.56 to 0.89). Sex-specific summary odds ratios were similar.

Conclusions: Cigarette smoking is associated with increased risks of adenocarcinomas of the esophagus and esophagogastric junction in white men and women; compared with current smoking, smoking cessation was associated with reduced risks.

Figure 1

The summary odds ratios and 95% confidence intervals (CI) for the association between cigarette smoking (ever vs never) and risk of cancer. A) Esophageal adenocarcinoma. B) Esophagogastric junctional adenocarcinoma. C) All adenocarcinoma. Summary odds ratios and 95% confidence intervals were estimated using a random-effects meta-analytic model. All statistical tests were two-sided. % Weight describes the weighting each study contributes to the summary odds ratio. The dot on each square represents the study-specific odds ratio, and the size of the surrounding square is an illustrative representation of study weighting. The horizontal lines represent the confidence intervals; if ending in an arrow, this indicates that the interval transcends the region plotted. The diamond represents the summary odds ratio and 95% confidence intervals. FINBAR = Factors Influencing the Barrett's Adenocarcinoma Relationship Study; LEO, Larynx, Esophagus, and Oral Cavity Study; NIH–AARP = National Institutes of Health–AARP; NSBES = Nova Scotia Barrett Esophagus Study.