Pancreatic ductal adenocarcinoma (PDAC) has an extremely poor prognosis, caused by various factors, such as the aggressiveness of the disease, the limited therapeutic options and the lack of early detection and risk markers. The ATP binding cassette subfamily C member 2 (ABCC2) protein plays a critical role in response to various drugs and is differentially expressed in gemcitabine sensitive and resistant cells. Moreover, single nucleotide polymorphisms (SNPs) in the gene have been associated with differential outcomes and prognosis in several tumour types. The aim of this study was to investigate the possible association between SNPs in the ABCC2 gene and overall survival (OS) in PDAC patients. We analysed 12 polymorphisms, including tagging-SNPs covering all the genetic variability of the ABCC2 gene and genotyped them in 1415 PDAC patients collected within the Pancreatic Disease ReseArch (PANDoRA) consortium. We tested the association between ABCC2 SNPs and PDAC OS using Cox proportional hazard models. We analysed PDAC patients dividing them by stage and observed that the minor alleles of three SNPs showed an association with worse OS [rs3740067: hazard ratio (HR) = 3.29, 95% confidence interval (CI) = 1.56-6.97, P = 0.002; rs3740073: HR = 3.11, 95% CI = 1.52-6.38, P = 0.002 and rs717620: HR = 2.90, 95% CI = 1.41-5.95, P = 0.004, respectively] in stage I patients. In patients with more advanced PDAC, we did not observe any statistically significant association. Our results suggest that rs3740067, rs3740073 and rs717620 could be promising prognostic markers in stage I PDAC patients.

1st Department of Medicine University of Szeged Szeged Hungary

ARC Net Research Centre University Hospital G B Rossi University of Verona Verona Italy

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

Department of Biology University of Pisa Pisa Italy

Department of Digestive Tract Diseases Medical University of Lodz Lodz Poland

Department of Gastroenterology Institute for Digestive Research Lithuanian University of Health Sciences Kaunas Lithuania

Department of General Visceral and Transplantation Surgery Heidelberg University Hospital Heidelberg Germany

Department of Surgery 1 Faculty of Medicine and Dentistry Palacky University Olomouc University Hospital Olomouc Czech Republic

Department of Surgery Gastroenterology and Oncology University of Padua Padua Italy

Department of Translational Medicine 1st Department of Medicine Medical School University of Pécs Pécs Hungary

Digestive and Liver Disease Unit S Andrea Hospital Rome Italy

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

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

Institute for Translational Medicine University of Pécs Pécs Hungary

Institute of Experimental Medicine Czech Academy of Sciences and Institute of Biology and Medical Genetics 1st Medical Faculty Charles University Prague Czech Republic

János Szentágothai Research Centre and Centre for Neuroscience University of Pécs Pécs Hungary

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

Pancreas Unit Department of Digestive System Sant'Orsola Malpighi Hospital Bologna Italy

Pancreatico Biliary Endoscopy and Endosonography Division Pancreas Translational and Clinical Research Center San Raffaele Scientific Institute Milan Italy

Translational Gastroenterology Research Group Hungarian Academy of Sciences and University of Szeged Szeged Hungary

Universitat Politècnica de Valéncia Valencia Spain

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