Abstract
Background:Diabetes is positively associated with various cancers, but its relationship with tumors of the esophagus/esophagogastric junction remains unclear.Methods:Data were harmonized across 13 studies in the International Barrett's and Esophageal Adenocarcinoma Consortium, comprising 2309 esophageal adenocarcinoma (EA) cases, 1938 esophagogastric junction adenocarcinoma (EGJA) cases, 1728 Barrett's esophagus (BE) cases, and 16,354 controls. Logistic regression was used to estimate study‐specific odds ratios (ORs) and 95% CIs for self‐reported diabetes in association with EA, EGJA, and BE. Adjusted ORs were then combined using random‐effects meta‐analysis.Results:Diabetes was associated with a 34% increased risk of EA (OR, 1.34; 95% CI, 1.00‐1.80; I2 = 48.8% [where 0% indicates no heterogeneity, and larger values indicate increasing heterogeneity between studies]), 27% for EGJA (OR, 1.27; 95% CI, 1.05‐1.55; I2 = 0.0%), and 30% for EA/EGJA combined (OR, 1.30; 95% CI, 1.06‐1.58; I2 = 34.9%). Regurgitation symptoms modified the diabetes‐EA/EGJA association (P for interaction = .04) with a 63% increased risk among participants with regurgitation (OR, 1.63; 95% CI, 1.19‐2.22), but not among those without regurgitation (OR, 1.03; 95% CI, 0.74‐1.43). No consistent association was found between diabetes and BE.Conclusions:Diabetes was associated with increased EA and EGJA risk, which was confined to individuals with regurgitation symptoms. Lack of an association between diabetes and BE suggests that diabetes may influence progression of BE to cancer.
Original language | English |
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Pages (from-to) | 4210-4223 |
Number of pages | 14 |
Journal | Cancer |
Volume | 125 |
Issue number | 23 |
Early online date | 6 Sept 2019 |
DOIs | |
Publication status | Published - 1 Dec 2019 |
Bibliographical note
Funding InformationNational Cancer Institute
National Institutes of Health. Grant Numbers: K23DK079291, R01CA001833, R01CA116845, K23DK059311, R01DK063616, K08DK002697, R01CA059636, R01CA030022, R37CA041530, U01CA057949, R01CA109193, U01CA199336, U54CA163059
Research & Development Office (Belfast, Northern Ireland)
Health Research Board (Dublin, Ireland)
Ulster Cancer Foundation
The Netherlands Cancer Foundation and the Dutch Digestive Disease Foundation
Queensland Cancer Fund
National Health and Medical Research Council
Kaiser Permanente Community Benefit Grant
California Tobacco Related Research Program. Grant Number: 3RT‐0122
US Department of Veteran's Affairs Clinical Science Research and Development. Grant Number: I01‐CX000899
Keywords
- Barrett esophagus
- diabetes
- epidemiology
- esophageal adenocarcinoma
- meta-analysis