Functional single nucleotide polymorphisms within the cyclin-dependent kinase inhibitor 2A/2B region affect pancreatic cancer risk
| Autor: | Ugo Boggi, Cosmeri Rizzato, Krzysztof Jamroziak, Andrea Mambrini, Gabriele Capurso, Yogesh K. Vashist, Valerio Pazienza, Christoph W. Michalski, Giulia Martina Cavestro, Keitaro Matsuo, Ewa Małecka-Panas, Jakob R. Izbicki, Harald Klüter, Timothy J. Key, Ludmila Vodickova, Vincenzo Corbo, Kenji Yamao, Domenica Gioffreda, Anna Stępień, Milena Di Leo, Willem Niesen, Audrius Ivanauskas, Cosimo Sperti, Carlo Federico Zambon, Peter Bugert, Beatrice Mohelnikova-Duchonova, Satoyo Hosono, Angelo Andriulli, Renata Talar-Wojnarowska, Maria Gazouli, John P. Neoptolemos, Franco Bambi, Francesca Tavano, Claudio Pasquali, Yasuhiro Shimizu, Manuela Pastore, Federico Canzian, Rudolf Kaaks, Daniele Campa, Gianfranco Delle Fave, Frederike Dijk, George Theodoropoulos, Raffaele Pezzilli, Paola Pacetti, Eithne Costello, Pavel Vodicka, Verena Katzke, Stefano Landi, Juozas Kupcinskas, Oliver Strobel, Martin Lovecek, Thilo Hackert, Manuel Gentiluomo, Markus W. Büchler, Pavel Soucek, Roberto Valente, Bas Bueno-de-Mesquita, Hidemi Ito, Kay-Tee Khaw, Olivier R. Busch, Daniela Basso |
|---|---|
| Přispěvatelé: | Campa, D, Pastore, M, Gentiluomo, M, Talar Wojnarowska, R, Kupcinskas, J, Malecka Panas, E, Neoptolemos, Jp, Niesen, W, Vodicka, P, Delle Fave, G, Bas Bueno de Mesquita, H, Gazouli, M, Pacetti, P, Di Leo, M, Ito, H, Klüter, H, Soucek, P, Corbo, V, Yamao, K, Hosono, S, Kaaks, R, Vashist, Y, Gioffreda, D, Strobel, O, Shimizu, Y, Dijk, F, Andriulli, A, Ivanauskas, A, Bugert, P, Tavano, F, Vodickova, L, Zambon, Cf, Lovecek, M, Landi, S, Key, Tj, Boggi, U, Pezzilli, R, Jamroziak, K, Mohelnikova Duchonova, B, Mambrini, A, Bambi, F, Busch, O, Pazienza, V, Valente, R, Theodoropoulos, G, Hackert, T, Capurso, G, Cavestro, GIULIA MARTINA, Pasquali, C, Basso, D, Sperti, C, Matsuo, K, Büchler, M, Khaw, Kt, Izbicki, J, Costello, E, Katzke, V, Michalski, C, Stepien, A, Rizzato, C, Canzian, F., CCA -Cancer Center Amsterdam, Pathology, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, Surgery |
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Pancreatic disease CDKN2A association study miRSNP pancreatic cancer single nucleotide polymorphisms Alleles Asian Continental Ancestry Group Binding Sites Carcinoma Pancreatic Ductal Case-Control Studies Cyclin-Dependent Kinase Inhibitor p15 Cyclin-Dependent Kinase Inhibitor p18 DNA Methylation Disease Progression European Continental Ancestry Group Genetic Predisposition to Disease Genotype Germ-Line Mutation Humans International Cooperation Japan Odds Ratio Pancreatic Neoplasms Prognosis Retrospective Studies Polymorphism Single Nucleotide Bioinformatics 0302 clinical medicine Medicine Single Nucleotide 3. Good health Oncology Pancreatic Ductal 030220 oncology & carcinogenesis Research Paper Single-nucleotide polymorphism White People 03 medical and health sciences Germline mutation Asian People Pancreatic cancer Allele Polymorphism Cyclin-Dependent Kinase Inhibitor p16 business.industry Carcinoma Cancer medicine.disease 030104 developmental biology Cancer research business |
| Zdroj: | Oncotarget, 7(35), 57011-57020. Impact Journals ONCOTARGET Oncotarget |
| ISSN: | 1949-2553 |
| Popis: | 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 (OR het=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/Blocus could represent a genetic link between diabetes and pancreatic cancer risk. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|