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Do pancreatic cancer and chronic pancreatitis share the same genetic risk factors? A PANcreatic Disease ReseArch (PANDoRA) consortium investigation

Campa D 1 , Pastore M 1 , Capurso G 2 , Hackert T 3 , Di Leo M 4 , Izbicki JR 5 Show all authors , Khaw KT 6 , Gioffreda D 7 , Kupcinskas J 8 , Pasquali C 9 , Macinga P 10 , Kaaks R 11 , Stigliano S 2 , Peeters PH 12 , Key TJ 13 , Talar-Wojnarowska R 14 , Vodicka P 10 , Valente R 2 , Vashist YK 5 , Salvia R 15 , Papaconstantinou I 16 , Shimizu Y 17 , Valsuani C 18 , Zambon CF 19 , Gazouli M 20 , Valantiene I 8 , Niesen W 3 , Mohelnikova-Duchonova B 21 , Hara K 22 , Soucek P 23 , Malecka-Panas E 14 , Bueno-de-Mesquita HBA 24 , Johnson T 11 , Brenner H 25 , Tavano F 7 , Fogar P 26 , Ito H 27 , Sperti C 9 , Butterbach K 25 , Latiano A 7 , Andriulli A 7 , Cavestro GM 4 , Busch ORC 28 , Dijk F 29 , Greenhalf W 30 , Matsuo K 27 , Lombardo C 31 , Strobel O 3 , König AK 3 , Cuk K 25 , Strothmann H 3 , Katzke V 11 , Cantore M 18 , Mambrini A 18 , Oliverius M 32 , Pezzilli R 33 , Landi S 1 , Canzian F 34

Affiliations 

  • 1 Department of Biology, University of Pisa, Pisa, Italy
  • 2 Digestive and Liver Disease Unit, S. Andrea Hospital 'Sapienza' University of Rome, Rome, Italy
  • 3 Department of General Surgery, University Hospital Heidelberg, Heidelberg, Germany
  • 4 Gastroenterology and Gastrointestinal Endoscopy Unit, Vita-Salute San Raffaele University, San Raffaele Scientific Institute, Milan, Italy
  • 5 Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
  • 6 Clinical Gerontology Unit, Addenbrooke's Hospital, University of Cambridge School of Clinical Medicine, Cambridge, United Kingdom
  • 7 Division of Gastroenterology and Research Laboratory, Department of Surgery, IRCCS Scientific Institute and Regional General Hospital "Casa Sollievo della Sofferenza", San Giovanni Rotondo, Italy
  • 8 Department of Gastroenterology, Lithuanian University of Health Sciences, Kaunas, Lithuania
  • 9 Department of Surgery, Oncology and Gastroenterology (DiSCOG), University of Padova, Padova, Italy
  • 10 Institute of Experimental Medicine, Czech Academy of Sciences and Institute of Clinical and Experimental Medicine, Prague, Czech Republic
  • 11 Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany
  • 12 Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands
  • 13 Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom
  • 14 Department of Digestive Tract Diseases, Medical University of Lodz, Lodz, Poland
  • 15 Department of Surgery, Pancreas Institute, University and Hospital Trust of Verona, Verona, Italy
  • 16 Second Department of Surgery, Aretaieion Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece
  • 17 Department of Gastroenterological Surgery, Aichi Cancer Center Hospital, Nagoya, Japan
  • 18 Oncological Department, Azienda USL Toscana Nord Ovest, Oncological Unit of Massa Carrara, Carrara, Massa and Carrara, Italy
  • 19 Department of Medicine (DIMED), University of Padova, Padova, Italy
  • 20 Department of Basic Medical Sciences, Laboratory of Biology, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece
  • 21 Department of Oncology, Palacky University Medical School and Teaching Hospital, Olomouc, Czech Republic
  • 22 Department of Gastroenterology, Aichi Cancer Center Hospital, Nagoya, Japan
  • 23 Biomedical Center, Faculty of Medicine in Pilsen, Charles University in Prague, Pilsen, Czech Republic
  • 24 Department for Determinants of Chronic Diseases (DCD), National Institute for Public Health and the Environment, Bilthoven, The Netherlands
  • 25 Division of Clinical Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany
  • 26 Department of Laboratory Medicine, University-Hospital of Padova, Padova, Italy
  • 27 Division of Molecular and Clinical Epidemiology, Aichi Cancer Center Research Institute, Nagoya, Japan
  • 28 Department of Surgery, Academic Medical Centre, Amsterdam, the Netherlands
  • 29 Department of Pathology, Academic Medical Centre, Amsterdam, the Netherlands
  • 30 Institute for Health Research, Liverpool Pancreas Biomedical Research Unit, University of Liverpool, Liverpool, United Kingdom
  • 31 Division of General and Transplant Surgery, University of Pisa, Pisa, Italy
  • 32 Transplant Surgery Department, Institute for Clinical and Experimental Medicine, Prague, Czech Republic
  • 33 Pancreas Unit, Department of Digestive Diseases and Internal Medicine Sant'Orsola-Malpighi Hospital, Bologna, Italy
  • 34 Genomic Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany
Int J Cancer, 2018 01 15;142(2):290-296.
PMID: 28913878 DOI: 10.1002/ijc.31047

Abstract

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.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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