BACKGROUND: The association among gallbladder disease, cholecystectomy, and pancreatic cancer is unclear. Moreover, time interval between gallbladder disease or cholecystectomy and pancreatic cancer diagnosis is not considered in most previous studies. AIM: To quantify the association among gallbladder disease, cholecystectomy, and pancreatic cancer, considering time since first diagnosis of gallbladder disease or cholecystectomy. METHODS: We used data from nine case-control studies within the Pancreatic Cancer Case-Control Consortium, including 5760 cases of adenocarcinoma of the exocrine pancreas and 8437 controls. We estimated pooled odds ratios and the corresponding 95% confidence intervals by estimating study-specific odds ratios through multivariable unconditional logistic regression models, and then pooling the obtained estimates using fixed-effects models. RESULTS: Compared with patients with no history of gallbladder disease, the pooled odds ratio of pancreatic cancer was 1.69 (95% confidence interval, 1.51-1.88) for patients reporting a history of gallbladder disease. The odds ratio was 4.90 (95% confidence interval, 3.45-6.97) for gallbladder disease diagnosed <2 years before pancreatic cancer diagnosis and 1.11 (95% confidence interval, 0.96-1.29) when ≥2 years elapsed. The pooled odds ratio was 1.64 (95% confidence interval, 1.43-1.89) for patients who underwent cholecystectomy, as compared to those without cholecystectomy. The odds ratio was 7.00 (95% confidence interval, 4.13-11.86) for a surgery <2 years before pancreatic cancer diagnosis and 1.28 (95% confidence interval, 1.08-1.53) for a surgery ≥2 years before. CONCLUSIONS: There appears to be no long-term effect of gallbladder disease on pancreatic cancer risk, and at most a modest one for cholecystectomy. The strong short-term association can be explained by diagnostic bias and reverse causation.

Cancer Center and Institute of Oncology Warsaw Poland

Cancer Epidemiology Unit National Cancer Institute Centro di Riferimento Oncologico IRCCS Aviano Italy

CIBER of Epidemiology and Public Health Madrid Spain

Dalla Lana School of Public Health University of Toronto Toronto Ontario Canada

Department of Biomedical and Clinical Sciences University of Milan

Department of Clinical Sciences and Community Health University of Milan Milan Italy

Department of Epidemiology and Biostatistics Memorial Sloan Kettering Cancer Center New York New York

Department of Epidemiology and Biostatistics School of Public Health Imperial College London London UK

Department of Epidemiology Harvard School of Public Health Boston Massachusetts USA

Department of Gastroenterology and Hepatology University Medical Center Utrecht Utrecht The Netherlands

Department of Health Sciences Research Medicine and Medical Genetics Mayo Clinic Rochester New York USA

Department of Hygiene Epidemiology and Medical Statistics School of Medicine University of Athens Athens Greece

Department of Oncology Istituto di Ricerche Farmacologiche Mario Negri IRCCS Milan Italy

Division of Epidemiology and Biostatistics IEO European Institute of Oncology IRCCS Milan Italy

Faculty of Health Catholic University Ružomberok Slovak Republic

Genetic and Molecular Epidemiology Group Spanish National Cancer Research Centre and CIBERONC Madrid Spain

Health Promotion Foundation Nadarzyn

Institute for Health and Biomedical Research ISABIAL UMH Alicante

Institute of Hygiene and Epidemiology 1st Faculty of Medicine Charles University and General University Hospital Prague Prague Czech Republic

International Agency for Research on Cancer Lyon France

National Institute for Public Health and the Environment Bilthoven

Public Health Women's and Children's Hospital Adelaide South Australia Australia

Regional Authority of Public Health Banská Bystrica Slovak Republic

The Tisch Cancer Institute Mount Sinai School of Medicine New York New York USA

Unit of Biomarkers and Susceptibility Oncology Data Analytics Program Catalan Institute of Oncology L'Hospitalet de Llobregat Barcelona Spain

Unit of Medical Statistics and Biometry National Cancer Institute IRCCS Foundation

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