Jessica L Petrick1, Nan Li2, Lesley A Anderson3, Leslie Bernstein4, Douglas A Corley5, Hashem B El Serag6, Sheetal Hardikar7,8, Linda M Liao1, Geoffrey Liu9, Liam J Murray3, Joel H Rubenstein10,11, Jennifer L Schneider5, Nicholas J Shaheen12, Aaron P Thrift13,14, Piet A van den Brandt15, Thomas L Vaughan16, David C Whiteman17, Anna H Wu18, Wei K Zhao5, Marilie D Gammon19, Michael B Cook1. 1. Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland. 2. Department of Epidemiology, Brown University School of Public Health, Providence, Rhode Island. 3. Center for Public Health, School of Medicine, Dentistry, and Biomedical Sciences, Queens University Belfast, Belfast, Northern Ireland. 4. Division of Biomarkers of Early Detection and Prevention, Department of Population Sciences, City of Hope Comprehensive Cancer Center, Duarte, California. 5. Division of Research, Kaiser Permanente, Northern California, Oakland, California. 6. Section of Gastroenterology and Hepatology, Department of Medicine, Baylor College of Medicine, Houston, Texas. 7. Department of Population Health Sciences, University of Utah, Salt Lake City, Utah. 8. Public Health Sciences Division, Fred Hutchinson Cancer Center, Seattle, Washington. 9. Princess Margaret Cancer Center, University Health Network, Toronto, Ontario, Canada. 10. Ann Arbor Veterans Affairs Center for Clinical Management Research, Ann Arbor, Michigan. 11. Barrett's Esophagus Program, Division of Gastroenterology, University of Michigan, Ann Arbor, Michigan. 12. Division of Gastroenterology and Hepatology, University of North Carolina, Chapel Hill, North Carolina. 13. Section of Epidemiology and Population Sciences, Department of Medicine, Baylor College of Medicine, Houston, Texas. 14. Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, Texas. 15. Department of Epidemiology, GROW School for Oncology and Biology, Maastricht University Medical Center, Maastricht, Netherlands. 16. Program in Cancer Epidemiology, Fred Hutchinson Cancer Center, Seattle, Washington. 17. Cancer Control, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia. 18. Department of Preventive Medicine, University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, California. 19. Department of Epidemiology, University of North Carolina, Chapel Hill, North Carolina.
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.
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.
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