Gastroesophageal reflux in relation to adenocarcinomas of the esophagus: a pooled analysis from the Barrett's and Esophageal Adenocarcinoma Consortium (BEACON)

• Published in: PloS one Vol. 9; no. 7; p. e103508
• Main Authors: Cook, Michael B, Corley, Douglas A, Murray, Liam J, Liao, Linda M, Kamangar, Farin, Ye, Weimin, Gammon, Marilie D, Risch, Harvey A, Casson, Alan G, Freedman, Neal D, Chow, Wong-Ho, Wu, Anna H, Bernstein, Leslie, Nyrén, Olof, Pandeya, Nirmala, Whiteman, David C, Vaughan, Thomas L
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 30-07-2014; Public Library of Science (PLoS)
• Subjects: Adenocarcinoma; Adenocarcinoma - etiology; Age Factors; Aged; Alcohol use; Analysis; Biology and Life Sciences; Body mass; Body Mass Index; Body size; Case-Control Studies; Cigarette smoking; Cigarettes; Consortia; Esophageal cancer; Esophageal Neoplasms - etiology; Esophagus; Female; Gastroesophageal reflux; Gastroesophageal Reflux - complications; Gastroesophageal Reflux - epidemiology; Health risk assessment; Heart; Humans; Logistic Models; Male; Medical research; Medicin och hälsovetenskap; Medicine and Health Sciences; Meta-analysis; Middle Aged; Odds Ratio; Pathogenesis; Regression analysis; Regurgitation; Research and Analysis Methods; Risk analysis; Risk Factors; Sensitivity analysis; Sex; Smoking; Socioeconomic factors; Statistical analysis; Studies; Sweden; California; Australia; United States > US; Maryland
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0103508

Previous 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.
Detailed 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.
Five 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.
This 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.