BACKGROUND: Esophageal adenocarcinoma is rapidly increasing in incidence. Body mass index (BMI) is a risk factor, but its distribution does not reflect the demographic distribution of the cancer (which is highest among White men). Abdominal obesity patterns may explain this discordance, but no studies exist to date. METHODS: Nested case-control study within 206,974 members of the Kaiser Permanente multiphasic health checkup cohort; subjects received detailed questionnaires, a standardized examination including BMI and anthropometric measurements, and follow-up of esophageal and cardia cancers using registry data. RESULTS: 101 incident esophageal adenocarcinomas, 105 cardia adenocarcinomas, and 144 esophageal squamous cell carcinomas were detected (BMI data available for all cases; abdominal measurements for a subset). Increasing abdominal diameter was strongly associated with an increased risk of esophageal adenocarcinoma [odds ratio (OR), 3.47; 95% confidence interval (95% CI), 1.29-9.33; abdominal diameter, > or =25 versus <20 cm]. Adjustment for BMI did not diminish this association (BMI-adjusted OR, 4.78; 95% CI, 1.14-20.11). The association was also not diminished by adjustment for gastroesophageal reflux-type symptoms, although reflux-type symptoms were separately associated with both abdominal diameter and cancer risk. Abdominal diameter was not associated with the risk of cardia adenocarcinomas (OR, 1.28; 95% CI, 0.38-4.25; diameter, > or =25 versus <20 cm) or esophageal squamous cell carcinomas (OR, 0.78; 95% CI, 0.32-1.92). CONCLUSIONS: Increasing abdominal diameter was associated with an increased risk of esophageal adenocarcinoma, independent of BMI. Cancer risk was not substantially mediated through gastroesophageal reflux-type symptoms, although symptoms may imperfectly measure reflux severity. Given abdominal obesity is more common among males, these findings suggest that increases in obesity may disproportionately increase the risk of esophageal adenocarcinoma in males.