Gastroesophageal Reflux in Relation to Adenocarcinomas of the Esophagus: A Pooled Analysis from the Barrett’s and Esophageal Adenocarcinoma Consortium (BEACON)
Open accessAbstract
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
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Both ERD and BE are considered precursor conditions to esophageal adenocarcinoma (EAC).
“Both ERD and BE are considered precursor conditions to esophageal adenocarcinoma (EAC)[41].”
From Proton pump inhibitors and dysbiosis: current knowledge and aspects to be clarified (2019) · cites this paper as [41]
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- Authors
- Cook, M. B., Corley, D. A., Murray, L. J., Liao, L. M., Kamangar, F., Ye, W., Gammon, M. D., Risch, H. A., Casson, A. G., Freedman, N. D., Chow, W.-H., Wu, A. H., Bernstein, L., Nyrén, O., Pandeya, N., Whiteman, D. C., & Vaughan, T. L.
- Affiliations
- United States Department of Health and Human Services (US)
- Kaiser Permanente (US)
- Queen's University Belfast (GB)
- Karolinska Institutet (SE)
- University of North Carolina at Chapel Hill (US)
- Yale University (US)
- University of Saskatchewan (CA)
- The University of Texas MD Anderson Cancer Center (US)
- University of Southern California (US)
- City Of Hope National Medical Center (US)
- QIMR Berghofer Medical Research Institute (AU)
- Fred Hutch Cancer Center (US)
- Corresponding author
- Cook, Michael B.
- ORCID
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2014-07-30
- Volume
- 9
- Issue
- 7
- Pages
- e103508
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC4116205
- OpenAlex
- W2071456214
- Cited by
- 165
- References
- 32
- Citations by year
- 2026: 7 · 2025: 7 · 2024: 8 · 2023: 14 · 2022: 15 · 2021: 10 · 2020: 16 · 2019: 21 · 2018: 13 · 2017: 22 · 2016: 14 · 2015: 15 · 2014: 3
- FWCI
- 17.84
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- PLoS ONE (publishedVersion, public-domain)
- Europe PMC (PubMed Central) (publishedVersion, public-domain)
- PubMed Central (publishedVersion, public-domain)
- PubMed (publishedVersion)
- Carolina Digital Repository (University of North Carolina at Chapel Hill) (submittedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- UNC Libraries
- Funders
- Health Research Board
- National Institutes of Health (3RT-0122, 10RT-0251)
- Medical Research Council (MR/K023241/1, 3RT-0122, 10RT-0251)
- National Health and Medical Research Council (199600, R01 CA57947-03, 10RT-0251, 3RT-0122)
- National Cancer Institute (R01 CA-57947-03, U01CA57949, CA57983, CA57949, R01CA057947, U01CA57923, R01CA059636, U01CA057949, CA59636, CA 57923, U01CA057923, U01CA57983, K05CA124911, U01CA057983)
- National Institute of Allergy and Infectious Diseases (R01AI057947)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK063616, R01 DK63616-01, R21DK077742)
- Topics
- Health Sciences › Medicine › Surgery › Esophageal Cancer Research and Treatment
- Health Sciences › Medicine › Gastroenterology › Gastroesophageal reflux and treatments
- Health Sciences › Medicine › Surgery › Esophageal and GI Pathology
- Keywords
- gastroesophageal reflux, esophageal adenocarcinoma, gastroesophageal junction adenocarcinoma, heartburn, regurgitation, symptom duration, symptom frequency, cancer risk factors, cigarette smoking, body mass index, sex differences, age differences
- MeSH terms
- Adenocarcinoma, Age Factors, Aged, Esophageal Neoplasms, Female, Gastroesophageal Reflux, Humans, Male, Middle Aged, Risk Factors, Smoking, Body Mass Index, Logistic Models, Odds Ratio, Case-Control Studies
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