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Functional single nucleotide polymorphisms within the cyclin-dependent kinase inhibitor 2A/2B region affect pancreatic cancer risk
D. Campa, M. Pastore, M. Gentiluomo, R. Talar-Wojnarowska, J. Kupcinskas, E. Malecka-Panas, JP. Neoptolemos, W. Niesen, P. Vodicka, G. Delle Fave, HB. Bueno-de-Mesquita, M. Gazouli, P. Pacetti, M. Di Leo, H. Ito, H. Klüter, P. Soucek, V. Corbo,...
Jazyk angličtina Země Spojené státy americké
Typ dokumentu časopisecké články
Grantová podpora
NV16-28375A
MZ0
CEP - Centrální evidence projektů
Digitální knihovna NLK
Plný text - Článek
NLK
Free Medical Journals
od 2010
Freely Accessible Journals
od 2010
PubMed Central
od 2010
Europe PubMed Central
od 2010
Open Access Digital Library
od 2010-01-01
- MeSH
- alely MeSH
- Asijci MeSH
- běloši MeSH
- duktální karcinom slinivky břišní genetika MeSH
- genetická predispozice k nemoci MeSH
- genotyp MeSH
- inhibitor p15 cyklin-dependentní kinasy genetika MeSH
- inhibitor p18 cyklin-dependentní kinasy genetika MeSH
- jednonukleotidový polymorfismus * MeSH
- lidé MeSH
- metylace DNA MeSH
- mezinárodní spolupráce MeSH
- nádory slinivky břišní diagnóza etnologie genetika MeSH
- odds ratio MeSH
- prognóza MeSH
- progrese nemoci MeSH
- retrospektivní studie MeSH
- studie případů a kontrol MeSH
- vazebná místa MeSH
- zárodečné mutace MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Japonsko MeSH
The CDKN2A (p16) gene plays a key role in pancreatic cancer etiology. It is one of the most commonly somatically mutated genes in pancreatic cancer, rare germline mutations have been found to be associated with increased risk of developing familiar pancreatic cancer and CDKN2A promoter hyper-methylation has been suggested to play a critical role both in pancreatic cancer onset and prognosis. In addition several unrelated SNPs in the 9p21.3 region, that includes the CDNK2A, CDNK2B and the CDNK2B-AS1 genes, are associated with the development of cancer in various organs. However, association between the common genetic variability in this region and pancreatic cancer risk is not clearly understood. We sought to fill this gap in a case-control study genotyping 13 single nucleotide polymorphisms (SNPs) in 2,857 pancreatic ductal adenocarcinoma (PDAC) patients and 6,111 controls in the context of the Pancreatic Disease Research (PANDoRA) consortium. We found that the A allele of the rs3217992 SNP was associated with an increased pancreatic cancer risk (ORhet=1.14, 95% CI 1.01-1.27, p=0.026, ORhom=1.30, 95% CI 1.12-1.51, p=0.00049). This pleiotropic variant is reported to be a mir-SNP that, by changing the binding site of one or more miRNAs, could influence the normal cell cycle progression and in turn increase PDAC risk. In conclusion, we observed a novel association in a pleiotropic region that has been found to be of key relevance in the susceptibility to various types of cancer and diabetes suggesting that the CDKN2A/B locus could represent a genetic link between diabetes and pancreatic cancer risk.
Blood Transfusion Service Azienda Ospedaliero Universitaria Meyer Florence Italy
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 Hematology Institute of Hematology and Transfusion Medicine Warsaw Poland
Department of Laboratory Medicine University Hospital of Padova Padova Italy
Department of Medicine DIMED 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 DiSCOG University of Padova Padova Italy
Digestive and Liver Disease Unit S Andrea Hospital 'Sapienza' University of Rome Rome Italy
Division Epidemiology and Prevention Aichi Cancer Center Research Institute Nagoya Japan
Division of Cancer Epidemiology German Cancer Research Center Heidelberg Germany
Division of General and Transplant Surgery Pisa University Hospital Pisa Italy
Division of Molecular Medicine Aichi Cancer Center Research Institute Nagoya Japan
Epidemiology Unit Nuffield Department of Population Health University of Oxford Oxford UK
Genomic Epidemiology Group German Cancer Research Center Heidelberg Germany
Laboratory of Clinical Transplant Immunology and Genetics Copernicus Memorial Hospital Lodz Poland
Oncological Department Massa Carrara Azienda USL Toscana Nord Ovest Carrara Italy
Pancreas Unit Department of Digestive System Dant'Orsola Malpighi Hospital Bologna Italy
Citace poskytuje Crossref.org
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- $a Campa, Daniele $u Department of Biology, University of Pisa, Pisa, Italy. Genomic Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany.
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- $a Functional single nucleotide polymorphisms within the cyclin-dependent kinase inhibitor 2A/2B region affect pancreatic cancer risk / $c D. Campa, M. Pastore, M. Gentiluomo, R. Talar-Wojnarowska, J. Kupcinskas, E. Malecka-Panas, JP. Neoptolemos, W. Niesen, P. Vodicka, G. Delle Fave, HB. Bueno-de-Mesquita, M. Gazouli, P. Pacetti, M. Di Leo, H. Ito, H. Klüter, P. Soucek, V. Corbo, K. Yamao, S. Hosono, R. Kaaks, Y. Vashist, D. Gioffreda, O. Strobel, Y. Shimizu, F. Dijk, A. Andriulli, A. Ivanauskas, P. Bugert, F. Tavano, L. Vodickova, CF. Zambon, M. Lovecek, S. Landi, TJ. Key, U. Boggi, R. Pezzilli, K. Jamroziak, B. Mohelnikova-Duchonova, A. Mambrini, F. Bambi, O. Busch, V. Pazienza, R. Valente, GE. Theodoropoulos, T. Hackert, G. Capurso, GM. Cavestro, C. Pasquali, D. Basso, C. Sperti, K. Matsuo, M. Büchler, KT. Khaw, J. Izbicki, E. Costello, V. Katzke, C. Michalski, A. Stepien, C. Rizzato, F. Canzian,
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- $a The CDKN2A (p16) gene plays a key role in pancreatic cancer etiology. It is one of the most commonly somatically mutated genes in pancreatic cancer, rare germline mutations have been found to be associated with increased risk of developing familiar pancreatic cancer and CDKN2A promoter hyper-methylation has been suggested to play a critical role both in pancreatic cancer onset and prognosis. In addition several unrelated SNPs in the 9p21.3 region, that includes the CDNK2A, CDNK2B and the CDNK2B-AS1 genes, are associated with the development of cancer in various organs. However, association between the common genetic variability in this region and pancreatic cancer risk is not clearly understood. We sought to fill this gap in a case-control study genotyping 13 single nucleotide polymorphisms (SNPs) in 2,857 pancreatic ductal adenocarcinoma (PDAC) patients and 6,111 controls in the context of the Pancreatic Disease Research (PANDoRA) consortium. We found that the A allele of the rs3217992 SNP was associated with an increased pancreatic cancer risk (ORhet=1.14, 95% CI 1.01-1.27, p=0.026, ORhom=1.30, 95% CI 1.12-1.51, p=0.00049). This pleiotropic variant is reported to be a mir-SNP that, by changing the binding site of one or more miRNAs, could influence the normal cell cycle progression and in turn increase PDAC risk. In conclusion, we observed a novel association in a pleiotropic region that has been found to be of key relevance in the susceptibility to various types of cancer and diabetes suggesting that the CDKN2A/B locus could represent a genetic link between diabetes and pancreatic cancer risk.
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