title: Association of genetic polymorphisms with survival of pancreatic ductal adenocarcinoma patients.
abstract: 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.
authors: Genomic Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany, Department of Translational Research and New Technologies in Medicine and Surgery and.
authors: Cosmeri
authors: C
authors: Rizzato
authors: Genomic Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany, Department of Biology, University of Pisa, Pisa, Italy.
authors: Daniele
authors: D
authors: Campa
authors: Department of Digestive Tract Diseases, Medical University of Łódź, Łódź, Poland.
authors: Renata
authors: R
authors: Talar-Wojnarowska
authors: Department of Molecular and Clinical Cancer Medicine, NIHR Liverpool Pancreas Biomedical Research Unit, University of Liverpool, Liverpool, UK.
authors: Christopher
authors: C
authors: Halloran
authors: Department of Gastroenterology, Lithuanian University of Health Sciences, Kaunas, Lithuania.
authors: Juozas
authors: J
authors: Kupcinskas
authors: Unit of Surgery B, The Pancreas Institute, Department of Surgery and Oncology, G.B. Rossi Hospital, University of Verona Hospital Trust, Verona, Italy.
authors: Giovanni
authors: G
authors: Butturini
authors: Department of Oncology, Palacky University Medical School and Teaching Hospital, Olomouc, Czech Republic.
authors: Beatrice
authors: B
authors: Mohelníková-Duchoňová
authors: Department of Surgery, Gastroenterology and Oncology, University of Padua, Padua, Italy.
authors: Cosimo
authors: C
authors: Sperti
authors: Department of General, Visceral and Transplantation Surgery, University Hospital Heidelberg, Heidelberg, Germany.
authors: Christine
authors: C
authors: Tjaden
authors: Department of Molecular and Clinical Cancer Medicine, NIHR Liverpool Pancreas Biomedical Research Unit, University of Liverpool, Liverpool, UK.
authors: Paula
authors: P
authors: Ghaneh
authors: Department of General, Visceral and Transplantation Surgery, University Hospital Heidelberg, Heidelberg, Germany.
authors: Thilo
authors: T
authors: Hackert
authors: Department of Translational Research and New Technologies in Medicine and Surgery and.
authors: Niccola
authors: N
authors: Funel
authors: Department of General, Visceral and Transplantation Surgery, University Hospital Heidelberg, Heidelberg, Germany.
authors: Nathalia
authors: N
authors: Giese
authors: Division of Gastroenterology and Research Laboratory, IRCCS Scientific Institute and Regional General Hospital "Casa Sollievo della Sofferenza", S. Giovanni Rotondo (FG), Italy.
authors: Francesca
authors: F
authors: Tavano
authors: Pancreas Unit, Department of Digestive Disease, Sant'Orsola-Malpighi Hospital, Bologna, Italy.
authors: Raffaele
authors: R
authors: Pezzilli
authors: Oncological Department, ASL 1 Massa Carrara, Massa Carrara, Italy.
authors: Mariangela
authors: M
authors: Pedata
authors: Department of Surgery, Gastroenterology and Oncology, University of Padua, Padua, Italy.
authors: Claudio
authors: C
authors: Pasquali
authors: Department of Basic Medical Science, Laboratory of Biology, School of Medicine, University of Athens, Athens, Greece.
authors: Maria
authors: M
authors: Gazouli
authors: Oncological Department, ASL 1 Massa Carrara, Massa Carrara, Italy.
authors: Andrea
authors: A
authors: Mambrini
authors: Department of Oncology, Palacky University Medical School and Teaching Hospital, Olomouc, Czech Republic.
authors: Pavel
authors: P
authors: Souček
authors: Department of Surgery, IRCCS Scientific Institute and Regional General Hospital "Casa Sollievo della Sofferenza", San Giovanni Rotondo (FG), Italy.
authors: Pierluigi
authors: P
authors: di Sebastiano
authors: Digestive and Liver Disease Unit, 'Sapienza' University of Rome, Rome, Italy.
authors: Gabriele
authors: G
authors: Capurso
authors: Oncological Department, ASL 1 Massa Carrara, Massa Carrara, Italy.
authors: Maurizio
authors: M
authors: Cantore
authors: Transplant Surgery Department, Institute for Clinical and Experimental Medicine, Prague, Czech Republic.
authors: Martin
authors: M
authors: Oliverius
authors: Division of Molecular Oncology of Gastrointestinal Tumors, German Cancer Research Center (DKFZ), Heidelberg, Germany and.
authors: Rienk
authors: R
authors: Offringa
authors: Department of Digestive Tract Diseases, Medical University of Łódź, Łódź, Poland.
authors: Ewa
authors: E
authors: Małecka-Panas
authors: Department of General, Visceral and Transplantation Surgery, University Hospital Heidelberg, Heidelberg, Germany.
authors: Oliver
authors: O
authors: Strobel
authors: ARC-NET, Centre for Applied Research on Cancer, University and Hospital Trust of Verona, Verona, Italy.
authors: Aldo
authors: A
authors: Scarpa
authors: Genomic Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany, f.canzian@dkfz.de.
authors: Federico
authors: F
authors: Canzian
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D000368:Aged; D021441:Carcinoma, Pancreatic Ductal / Q000235:genetics* / Q000473:pathology; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics*; D018572:Disease-Free Survival; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D051178:alpha Catenin / Q000235:genetics*
chemical_list: C079671:CTNNA2 protein, human; D050659:Core Binding Factor Alpha 1 Subunit; C493709:RUNX2 protein, human; D051178:alpha Catenin