R G P J de Jong1, A M Burden2, S de Kort3, M P P van Herk-Sukel4, P A J Vissers5, P K C Janssen6, H R Haak7, A A M Masclee3, F de Vries8, M L G Janssen-Heijnen9. 1. Department of Internal Medicine, VieCuri Medical Centre, Venlo, The Netherlands; Department of Internal Medicine, Division of Gastroenterology and Hepatology, GROW - School for Oncology and Developmental Biology, Maastricht University Medical Centre+, Maastricht, The Netherlands. Electronic address: roy.dejong@maastrichtuniversity.nl. 2. Department of Clinical Pharmacy and Toxicology, Maastricht University Medical Centre+, Maastricht, The Netherlands; Utrecht Institute for Pharmaceutical Sciences, Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht University, Utrecht, The Netherlands. 3. Department of Internal Medicine, Division of Gastroenterology and Hepatology, NUTRIM - School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Centre+, Maastricht, The Netherlands. 4. PHARMO Institute for Drug Outcomes Research, Utrecht, The Netherlands. 5. Department of Research, Netherlands Comprehensive Cancer Organization, Utrecht, The Netherlands. 6. Department of Clinical Pharmacy and Toxicology, Maastricht University Medical Centre+, Maastricht, The Netherlands; Utrecht Institute for Pharmaceutical Sciences, Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht University, Utrecht, The Netherlands; Utrecht Institute for Pharmaceutical Sciences, Division of Pharmacology, Utrecht University, Utrecht, The Netherlands; Department of Central Hospital Pharmacy, VieCuri Medical Centre, Venlo, The Netherlands. 7. Department of Internal Medicine, Máxima Medical Centre Eindhoven, Eindhoven, The Netherlands; Department of Internal Medicine, Division of General Internal Medicine, Maastricht University Medical Centre+, Maastricht, The Netherlands; Department of Health Services Research, CAPHRI School for Public Health and Primary Care, Maastricht University Medical Centre+, Maastricht, The Netherlands. 8. Department of Clinical Pharmacy and Toxicology, Maastricht University Medical Centre+, Maastricht, The Netherlands; Utrecht Institute for Pharmaceutical Sciences, Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht University, Utrecht, The Netherlands; Department of Health Services Research, CAPHRI School for Public Health and Primary Care, Maastricht University Medical Centre+, Maastricht, The Netherlands; MRC Life-course Epidemiology Unit, University of Southampton, Southampton, United Kingdom. 9. Department of Epidemiology, GROW - School for Oncology and Developmental Biology, Maastricht University Medical Centre+, Maastricht, The Netherlands; Department of Clinical Epidemiology, VieCuri Medical Centre, Venlo, The Netherlands.
Abstract
BACKGROUND: Type 2 diabetes mellitus (T2DM) may be a risk factor for gastrointestinal (GI) cancers, but variations in study designs of observational studies may have yielded biased results due to detection bias. Furthermore, differences in risk for GI cancer subsites have not been extensively evaluated. We aimed to determine the risk of GI cancer and its subsites in patients with T2DM and how it is affected by detection bias. METHODS: A matched cohort study was performed using the NCR-PHARMO database. New-users of ≥1 non-insulin anti-diabetic drug during 1998-2011 were matched with non-diabetic controls by year of birth, sex, and time between database entry and index. Cox regression analyses were performed with and without lag-period to estimate hazard ratios (HRs) for GI cancer and its subsites. Covariables included age, sex, use of other drugs and history of hospitalisation. RESULTS: An increased risk of GI cancer was observed in T2DM patients (HR 1.5, 95% confidence interval [CI] 1.3-1.7) compared with controls, which was attenuated in the 1-year lagged analysis (HR 1.4, 95% CI 1.2-1.7). Stratified by subsite, statistically significant increased risks of pancreatic (HR 4.7, 95% CI 3.1-7.2), extrahepatic bile duct (HR 4.2, 95% CI 1.5-11.8) and distal colon cancer (HR 1.5, 95% CI 1.1-2.1) were found, which remained statistically significantly increased in the lagged analysis. CONCLUSIONS: T2DM patients had a 40% increased risk of GI cancer. Increased GI cancer risks tended to be weaker when reducing detection bias by applying a 1-year lag-period. Future observational studies should therefore include sensitivity analyses in which this bias is minimised.
BACKGROUND:Type 2 diabetes mellitus (T2DM) may be a risk factor for gastrointestinal (GI) cancers, but variations in study designs of observational studies may have yielded biased results due to detection bias. Furthermore, differences in risk for GI cancer subsites have not been extensively evaluated. We aimed to determine the risk of GI cancer and its subsites in patients with T2DM and how it is affected by detection bias. METHODS: A matched cohort study was performed using the NCR-PHARMO database. New-users of ≥1 non-insulin anti-diabetic drug during 1998-2011 were matched with non-diabetic controls by year of birth, sex, and time between database entry and index. Cox regression analyses were performed with and without lag-period to estimate hazard ratios (HRs) for GI cancer and its subsites. Covariables included age, sex, use of other drugs and history of hospitalisation. RESULTS: An increased risk of GI cancer was observed in T2DM patients (HR 1.5, 95% confidence interval [CI] 1.3-1.7) compared with controls, which was attenuated in the 1-year lagged analysis (HR 1.4, 95% CI 1.2-1.7). Stratified by subsite, statistically significant increased risks of pancreatic (HR 4.7, 95% CI 3.1-7.2), extrahepatic bile duct (HR 4.2, 95% CI 1.5-11.8) and distal colon cancer (HR 1.5, 95% CI 1.1-2.1) were found, which remained statistically significantly increased in the lagged analysis. CONCLUSIONS: T2DM patients had a 40% increased risk of GI cancer. Increased GI cancer risks tended to be weaker when reducing detection bias by applying a 1-year lag-period. Future observational studies should therefore include sensitivity analyses in which this bias is minimised.
Authors: Inna Y Gong; Matthew C Cheung; Stephanie Read; Yingbo Na; Iliana C Lega; Lorraine L Lipscombe Journal: Diabetologia Date: 2021-01-06 Impact factor: 10.122
Authors: Laura Del Puerto-Nevado; Pablo Minguez; Marta Corton; Sonia Solanes-Casado; Isabel Prieto; Sebastian Mas; Ana Belen Sanz; Paula Gonzalez-Alonso; Cristina Villaverde; Sergio Portal-Nuñez; Oscar Aguilera; Carmen Gomez-Guerrero; Pedro Esbrit; Fernando Vivanco; Nieves Gonzalez; Carmen Ayuso; Alberto Ortiz; Federico Rojo; Jesus Egido; Gloria Alvarez-Llamas; Jesus Garcia-Foncillas Journal: Mol Oncol Date: 2019-02-16 Impact factor: 6.603