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Do pancreatic cancer and chronic pancreatitis share the same genetic risk factors? A PANcreatic Disease ReseArch (PANDoRA) consortium investigation
D. Campa, M. Pastore, G. Capurso, T. Hackert, M. Di Leo, JR. Izbicki, KT. Khaw, D. Gioffreda, J. Kupcinskas, C. Pasquali, P. Macinga, R. Kaaks, S. Stigliano, PH. Peeters, TJ. Key, R. Talar-Wojnarowska, P. Vodicka, R. Valente, YK. Vashist, R....
Language English Country United States
Document type Journal Article, Research Support, Non-U.S. Gov't
Grant support
NV16-28375A
MZ0
CEP Register
PubMed
28913878
DOI
10.1002/ijc.31047
Knihovny.cz E-resources
- MeSH
- Adenocarcinoma genetics pathology MeSH
- Pancreatitis, Chronic genetics pathology MeSH
- Adult MeSH
- Carcinoma, Pancreatic Ductal genetics pathology MeSH
- Nuclear Proteins genetics MeSH
- Polymorphism, Single Nucleotide * MeSH
- Middle Aged MeSH
- Humans MeSH
- Biomarkers, Tumor genetics MeSH
- Pancreatic Neoplasms genetics pathology MeSH
- Follow-Up Studies MeSH
- Prognosis MeSH
- Retrospective Studies MeSH
- Risk Factors MeSH
- Aged MeSH
- Case-Control Studies MeSH
- Trypsin genetics MeSH
- Trypsinogen genetics MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
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.
Biomedical Center Faculty of Medicine in Pilsen Charles University Prague Pilsen Czech Republic
Department of Biology University of Pisa Pisa Italy
Department of Digestive Tract Diseases Medical University of Lodz Lodz Poland
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 Laboratory Medicine University Hospital of Padova Padova Italy
Department of Medicine University of Padova Padova Italy
Department of Pathology Academic Medical Centre Amsterdam the Netherlands
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
Digestive and Liver Disease Unit S Andrea Hospital 'Sapienza' University of Rome Rome Italy
Division of Cancer Epidemiology German Cancer Research Center Heidelberg Germany
Division of Clinical Epidemiology German Cancer Research Center Heidelberg Germany
Genomic Epidemiology Group German Cancer Research Center Heidelberg Germany
Transplant Surgery Department Institute for Clinical and Experimental Medicine Prague Czech Republic
References provided by Crossref.org
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- $a 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.
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