Germline genetic variability might contribute, at least partially, to the survival of pancreatic ductal adenocarcinoma (PDAC) patients. Two recently performed genome-wide association studies (GWAS) on PDAC overall survival (OS) suggested (P < 10(-5)) the association between 30 genomic regions and PDAC OS. With the aim to highlight the true associations within these regions, we analyzed 44 single-nucleotide polymorphisms (SNPs) in the 30 candidate regions in 1722 PDAC patients within the PANcreatic Disease ReseArch (PANDoRA) consortium. We observed statistically significant associations for five of the selected regions. One association in the CTNNA2 gene on chromosome 2p12 [rs1567532, hazard ratio (HR) = 1.75, 95% confidence interval (CI) 1.19-2.58, P = 0.005 for homozygotes for the minor allele] and one in the last intron of the RUNX2 gene on chromosome 6p21 (rs12209785, HR = 0.88, 95% CI 0.80-0.98, P = 0.014 for heterozygotes) are of particular relevance. These loci do not coincide with those that showed the strongest associations in the previous GWAS. In silico analysis strongly suggested a possible mechanistic link between these two SNPs and pancreatic cancer survival. Functional studies are warranted to confirm the link between these genes (or other genes mapping in those regions) and PDAC prognosis in order to understand whether these variants may have the potential to impact treatment decisions and design of clinical trials.

ARC NET Centre for Applied Research on Cancer University and Hospital Trust of Verona Verona Italy

Department of Basic Medical Science Laboratory of Biology School of Medicine University of Athens Athens Greece

Department of Digestive Tract Diseases Medical University of Łódź Łódź Poland

Department of Gastroenterology Lithuanian University of Health Sciences Kaunas Lithuania

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

Department of Molecular and Clinical Cancer Medicine NIHR Liverpool Pancreas Biomedical Research Unit University of Liverpool Liverpool UK

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

Department of Surgery Gastroenterology and Oncology University of Padua Padua Italy

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

Department of Translational Research and New Technologies in Medicine and Surgery and

Digestive and Liver Disease Unit 'Sapienza' University of Rome Rome Italy

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

Division of Molecular Oncology of Gastrointestinal Tumors German Cancer Research Center Heidelberg Germany and

Genomic Epidemiology Group German Cancer Research Center Heidelberg Germany

Genomic Epidemiology Group German Cancer Research Center Heidelberg Germany Department of Biology University of Pisa Pisa Italy

Genomic Epidemiology Group German Cancer Research Center Heidelberg Germany Department of Translational Research and New Technologies in Medicine and Surgery and

Oncological Department ASL 1 Massa Carrara Massa Carrara Italy

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

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

Unit of Surgery B The Pancreas Institute Department of Surgery and Oncology G B Rossi Hospital University of Verona Hospital Trust Verona Italy

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Lack of association of CD44-rs353630 and CHI3L2-rs684559 with pancreatic ductal adenocarcinoma survival