@article{3101426,
    title = "Functional single nucleotide polymorphisms within the cyclindependent kinase inhibitor 2A/2B region affect pancreatic cancer risk",
    author = "Campa, D. and Pastore, M. and Gentiluomo, M. and Talar-Wojnarowska, R. and Kupcinskas, J. and Malecka-Panas, E. and Neoptolemos, J.P. and Niesen, W. and Vodicka, P. and Delle Fave, G. and Bas Bueno-de-Mesquita, H. and Gazouli, M. and Pacetti, P. and Di Leo, M. and Ito, H. and Klüter, H. and Soucek, P. and Corbo, V. and Yamao, K. and Hosono, S. and Kaaks, R. and Vashist, Y. and Gioffreda, D. and Strobel, O. and Shimizu, Y. and Dijk, F. and Andriulli, A. and Ivanauskas, A. and Bugert, P. and Tavano, F. and Vodickova, L. and Zambon, C.F. and Lovecek, M. and Landi, S. and Key, T.J. and Boggi, U. and Pezzilli, R. and Jamroziak, K. and Mohelnikova-Duchonova, B. and Mambrini, A. and Bambi, F. and Busch, O. and Pazienza, V. and Valente, R. and Theodoropoulos, G.E. and Hackert, T. and Capurso, G. and Cavestro, G.M. and Pasquali, C. and Basso, D. and Sperti, C. and Matsuo, K. and Büchler, M. and Khaw, K.-T. and Izbicki, J. and Costello, E. and Katzke, V. and Michalski, C. and Stepien, A. and Rizzato, C. and Canzian, F.",
    journal = "OncoTargets and therapy",
    year = "2016",
    volume = "7",
    number = "35",
    pages = "57011-57020",
    publisher = "Impact Journals, LLC",
    doi = "10.18632/oncotarget.10935",
    keywords = "microRNA;  CDKN2A protein, human;  CDKN2B protein, human;  cyclin dependent kinase inhibitor 2B;  cyclin dependent kinase inhibitor 2C, adult;  aged;  allele;  Article;  binding site;  cancer risk;  cancer susceptibility;  case control study;  CDKN2A gene;  CDKN2B gene;  cell cycle progression;  controlled study;  female;  gene;  gene function;  genetic association;  genetic risk;  genetic susceptibility;  genotype;  human;  major clinical study;  male;  pancreas adenocarcinoma;  pleiotropy;  single nucleotide polymorphism;  Asian continental ancestry group;  Caucasian;  disease exacerbation;  DNA methylation;  ethnology;  genetic predisposition;  genetics;  germline mutation;  international cooperation;  Japan;  odds ratio;  pancreas carcinoma;  pancreas tumor;  prognosis;  retrospective study, Alleles;  Asian Continental Ancestry Group;  Binding Sites;  Carcinoma, Pancreatic Ductal;  Case-Control Studies;  Cyclin-Dependent Kinase Inhibitor p15;  Cyclin-Dependent Kinase Inhibitor p18;  Disease Progression;  DNA Methylation;  European Continental Ancestry Group;  Genetic Predisposition to Disease;  Genotype;  Germ-Line Mutation;  Humans;  International Cooperation;  Japan;  Odds Ratio;  Pancreatic Neoplasms;  Polymorphism, Single Nucleotide;  Prognosis;  Retrospective Studies",
    abstract = "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."
}