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Background & Aims: A history of high body mass index (BMI) is associated strongly with a risk of esophageal adenocarcinoma (EAC). We investigated whether gastroesophageal reflux is involved in this association., Methods: We analyzed data from a population-based Swedish nationwide study of patients with a new diagnosis of EAC (n = 189) or gastroesophageal junction adenocarcinoma (n = 262), and matched controls (n = 816), from 1995 through 1997. Our analysis included data on BMI 20 years before study inclusion; maximum adult BMI; frequency, severity, and duration of gastroesophageal reflux symptoms; tumor features; and covariates (sex, age, smoking, alcohol, fruit and vegetable intake, and socioeconomic status). We conducted stratified analyses and synergy tests, adjusting for covariates., Results: Odds ratios (ORs) for EAC among subjects with a BMI of 25 or higher 20 years before inclusion, compared with those with a BMI less than 25, did not differ significantly, without or with adjustment for gastroesophageal reflux frequency (OR, 3.1; 95% confidence interval [CI], 2.2-4.4; and OR, 3.3; 95% CI, 2.2-4.8, respectively), severity (OR, 3.3; 95% CI, 2.2-4.8), or duration (OR, 3.2; 95% CI, 2.2-4.7). However, there were interactions between BMI and categories of gastroesophageal reflux. BMI appeared to have the largest effect on gastroesophageal reflux frequency (synergy index, 8.9; 95% CI, 2.3-34.1 for maximum BMI; and gastroesophageal reflux >3 times/wk)., Conclusions: Based on a population-based study, the association between BMI and EAC does not appear to be affected by symptomatic gastroesophageal reflux, although there appears to be synergy between BMI and reflux., (Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.)