Abstract
BackgroundPrevious studies have evidenced an association between gastroesophageal reflux and esophageal adenocarcinoma (EA). It is unknown to what extent these associations vary by population, age, sex, body mass index, and cigarette smoking, or whether duration and frequency of symptoms interact in predicting risk. The Barrett’s and Esophageal Adenocarcinoma Consortium (BEACON) allowed an in-depth assessment of these issues.MethodsDetailed information on heartburn and regurgitation symptoms and covariates were available from five BEACON case-control studies of EA and esophagogastric junction adenocarcinoma (EGJA). We conducted single-study multivariable logistic regressions followed by random-effects meta-analysis. Stratified analyses, meta-regressions, and sensitivity analyses were also conducted.ResultsFive studies provided 1,128 EA cases, 1,229 EGJA cases, and 4,057 controls for analysis. All summary estimates indicated positive, significant associations between heartburn/regurgitation symptoms and EA. Increasing heartburn duration was associated with increasing EA risk; odds ratios were 2.80, 3.85, and 6.24 for symptom durations of <10 years, 10 to <20 years, and ≥20 years. Associations with EGJA were slighter weaker, but still statistically significant for those with the highest exposure. Both frequency and duration of heartburn/regurgitation symptoms were independently associated with higher risk. We observed similar strengths of associations when stratified by age, sex, cigarette smoking, and body mass index.ConclusionsThis analysis indicates that the association between heartburn/regurgitation symptoms and EA is strong, increases with increased duration and/or frequency, and is consistent across major risk factors. Weaker associations for EGJA suggest that this cancer site has a dissimilar pathogenesis or represents a mixed population of patients.
Highlights
The association between gastroesophageal reflux and inflammation of the distal esophageal mucosa was first expounded by Winkelstein in 1935 [1]
The work is made available under the Creative Commons CC0 public domain dedication
We assessed whether heartburn and regurgitation exposures were associated with esophageal adenocarcinoma (EA) and esophagogastric junction adenocarcinoma (EGJA) by pooling, harmonizing, and analyzing detailed individual participant data from five casecontrol studies in the international Barrett’s and Esophageal Adenocarcinoma Consortium (BEACON, http://beacon.tlvnet. net/)
Summary
The association between gastroesophageal reflux and inflammation of the distal esophageal mucosa was first expounded by Winkelstein in 1935 [1]. Barrett himself acknowledged that gastroesophageal reflux may be a cause of the eponymously titled metaplastic lesion that precedes adenocarcinoma [2], and future human observations [3] and animal experiments [4] were to provide evidence for such. Concurrent with these developments was the proposition, derived from clinical observation, that gastroesophageal reflux may predispose to cancer of the distal esophagus [5]. It is unknown to what extent these associations vary by population, age, sex, body mass index, and cigarette smoking, or whether duration and frequency of symptoms interact in predicting risk. The Barrett’s and Esophageal Adenocarcinoma Consortium (BEACON) allowed an in-depth assessment of these issues
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