Pancreatic ductal adenocarcinoma (PDAC) is a very aggressive tumor with a five-year survival of less than 6%. Chronic pancreatitis (CP), an inflammatory process in of the pancreas, is a strong risk factor for PDAC. Several genetic polymorphisms have been discovered as susceptibility loci for both CP and PDAC. Since CP and PDAC share a consistent number of epidemiologic risk factors, the aim of this study was to investigate whether specific CP risk loci also contribute to PDAC susceptibility. We selected five common SNPs (rs11988997, rs379742, rs10273639, rs2995271 and rs12688220) that were identified as susceptibility markers for CP and analyzed them in 2,914 PDAC cases, 356 CP cases and 5,596 controls retrospectively collected in the context of the international PANDoRA consortium. We found a weak association between the minor allele of the PRSS1-PRSS2-rs10273639 and an increased risk of developing PDAC (ORhomozygous = 1.19, 95% CI 1.02-1.38, p = 0.023). Additionally all the SNPs confirmed statistically significant associations with risk of developing CP, the strongest being PRSS1-PRSS2-rs10273639 (ORheterozygous = 0.51, 95% CI 0.39-0.67, p = 1.10 × 10-6 ) and MORC4-rs 12837024 (ORhomozygous = 2.07 (1.55-2.77, ptrend = 0.7 × 10-11 ). Taken together, the results from our study do not support variants rs11988997, rs379742, rs10273639, rs2995271 and rs12688220 as strong predictors of PDAC risk, but further support the role of these SNPs in CP susceptibility. Our study suggests that CP and PDAC probably do not share genetic susceptibility, at least in terms of high frequency variants.

2nd Department of Surgery Aretaieion Hospital School of Medicine National and Kapodistrian University of Athens Athens Greece

Biomedical Center Faculty of Medicine in Pilsen Charles University Prague Pilsen Czech Republic

Cancer Epidemiology Unit Nuffield Department of Population Health University of Oxford Oxford United Kingdom

Clinical Gerontology Unit Addenbrooke's Hospital University of Cambridge School of Clinical Medicine Cambridge United Kingdom

Department for Determinants of Chronic Diseases National Institute for Public Health and the Environment Bilthoven The Netherlands

Department of Basic Medical Sciences Laboratory of Biology School of Medicine National and Kapodistrian University of Athens Athens Greece

Department of Biology University of Pisa Pisa Italy

Department of Digestive Tract Diseases Medical University of Lodz Lodz Poland

Department of Epidemiology and Biostatistics The School of Public Health Imperial College London St Mary's Campus London United Kingdom

Department of Epidemiology Julius Center for Health Sciences and Primary Care University Medical Center Utrecht Utrecht The Netherlands

Department of Epidemiology Nagoya University Graduate School of Medicine Nagoya Japan

Department of Gastroenterological Surgery Aichi Cancer Center Hospital Nagoya Japan

Department of Gastroenterology Aichi Cancer Center Hospital Nagoya Japan

Department of Gastroenterology Lithuanian University of Health Sciences Kaunas Lithuania

Department of General Surgery University Hospital Heidelberg Heidelberg Germany

Department of General Visceral and Thoracic Surgery University Medical Center Hamburg Eppendorf Hamburg Germany

Department of Laboratory Medicine University Hospital of Padova Padova Italy

Department of Medicine University of Padova Padova Italy

Department of Oncology Palacky University Medical School and Teaching Hospital Olomouc Czech Republic

Department of Pathology Academic Medical Centre Amsterdam the Netherlands

Department of Social and Preventive Medicine Faculty of Medicine University of Malaya Kuala Lumpur Malaysia

Department of Surgery Academic Medical Centre Amsterdam the Netherlands

Department of Surgery Oncology and Gastroenterology University of Padova Padova Italy

Department of Surgery Pancreas Institute University and Hospital Trust of Verona Verona Italy

Department of Visceral Surgery Kantonsspital Aarau AG Aarau Switzerland

Digestive and Liver Disease Unit S Andrea Hospital 'Sapienza' University of Rome Rome Italy

Dipartimento di Ricerca Traslazionale e delle Nuove Tecnologie in Medicina e Chirurgia University of Pisa Pisa Italy

Division of Cancer Epidemiology German Cancer Research Center Heidelberg Germany

Division of Clinical Epidemiology German Cancer Research Center Heidelberg Germany

Division of Gastroenterology and Research Laboratory Department of Surgery IRCCS Scientific Institute and Regional General Hospital Casa Sollievo della Sofferenza San Giovanni Rotondo Italy

Division of General and Transplant Surgery University of Pisa Pisa Italy

Division of Molecular and Clinical Epidemiology Aichi Cancer Center Research Institute Nagoya Japan

Division of Preventive Oncology German Cancer Research Center Heidelberg Germany

Gastroenterology and Gastrointestinal Endoscopy Unit Vita Salute San Raffaele University San Raffaele Scientific Institute Milan Italy

Genomic Epidemiology Group German Cancer Research Center Heidelberg Germany

German Cancer Consortium Heidelberg Germany

Institute for Health Research Liverpool Pancreas Biomedical Research Unit University of Liverpool Liverpool United Kingdom

Institute of Experimental Medicine Czech Academy of Sciences and Institute of Clinical and Experimental Medicine Prague Czech Republic

MRC PHE Centre for Environment and Health Department of Epidemiology and Biostatistics School of Public Health Imperial College London United Kingdom

Oncological Department Azienda USL Toscana Nord Ovest Oncological Unit of Massa Carrara Carrara Massa and Carrara Italy

Pancreas Unit Department of Digestive Diseases and Internal Medicine Sant'Orsola Malpighi Hospital Bologna Italy

Transplant Surgery Department Institute for Clinical and Experimental Medicine Prague Czech Republic

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Genetic Susceptibility in Understanding of Pancreatic Ductal Adenocarcinoma Risk: A Decade-Long Effort of the PANDORA Consortium