title: Gastroesophageal reflux in relation to adenocarcinomas of the esophagus: a pooled analysis from the Barrett's and Esophageal Adenocarcinoma Consortium (BEACON).
abstract: 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.
authors: Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda, Maryland, United States of America.
authors: Michael B
authors: MB
authors: Cook
authors: Division of Research and Oakland Medical Center, Kaiser Permanente, Northern California, Oakland, California, United States of America.
authors: Douglas A
authors: DA
authors: Corley
authors: Centre for Public Health, Queen's University, Belfast, Northern Ireland.
authors: Liam J
authors: LJ
authors: Murray
authors: Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda, Maryland, United States of America.
authors: Linda M
authors: LM
authors: Liao
authors: Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda, Maryland, United States of America; Department of Public Health Analysis, School of Community Health and Policy, Morgan State University, Baltimore, Maryland, United States of America.
authors: Farin
authors: F
authors: Kamangar
authors: Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
authors: Weimin
authors: W
authors: Ye
authors: Department of Epidemiology, University of North Carolina School of Public Health, Chapel Hill, North Carolina, United States of America.
authors: Marilie D
authors: MD
authors: Gammon
authors: Yale University School of Medicine, Department of Epidemiology and Public Health, New Haven, Connecticut, United States of America.
authors: Harvey A
authors: HA
authors: Risch
authors: Department of Surgery, University of Saskatchewan, Saskatoon, Saskatchewan, Canada.
authors: Alan G
authors: AG
authors: Casson
authors: Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda, Maryland, United States of America.
authors: Neal D
authors: ND
authors: Freedman
authors: The University of Texas MD Anderson Cancer Center, Department of Epidemiology, Houston, Texas, United States of America.
authors: Wong-Ho
authors: WH
authors: Chow
authors: Department of Preventive Medicine, Keck School of Medicine, University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, California, United States of America.
authors: Anna H
authors: AH
authors: Wu
authors: Department of Population Sciences, Beckman Research Institute and City of Hope Comprehensive Cancer Center, Duarte, California, United States of America.
authors: Leslie
authors: L
authors: Bernstein
authors: Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
authors: Olof
authors: O
authors: Nyrén
authors: QIMR Berghofer Medical Research Institute, Brisbane, Australia.
authors: Nirmala
authors: N
authors: Pandeya
authors: QIMR Berghofer Medical Research Institute, Brisbane, Australia.
authors: David C
authors: DC
authors: Whiteman
authors: Program in Epidemiology, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.
authors: Thomas L
authors: TL
authors: Vaughan
mesh_terms: D000230:Adenocarcinoma / Q000209:etiology*; D000367:Age Factors; D000368:Aged; D015992:Body Mass Index; D016022:Case-Control Studies; D004938:Esophageal Neoplasms / Q000209:etiology*; D005260:Female; D005764:Gastroesophageal Reflux / Q000150:complications / Q000453:epidemiology*; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D012307:Risk Factors; D012907:Smoking