Περίληψη:
Pancreatic neuroendocrine tumors (PNETs) are heterogeneous neoplasms which represent only 2% of all pancreatic neoplasms by incidence, but 10% by prevalence. Genetic risk factors could have an important role in the disease aetiology, however only a small number of case control studies have been performed yet. To further our knowledge, we genotyped 13 SNPs belonging to the pleiotropic CDKN2A/B gene region in 320 PNET cases and 4436 controls, the largest study on the disease so far. We observed a statistically significant association between the homozygotes for the minor allele of the rs2518719 SNP and an increased risk of developing PNET (ORhom = 2.08, 95% CI 1.05-4.11, p = 0.035). This SNP is in linkage disequilibrium with another polymorphic variant associated with increased risk of several cancer types. In silico analysis suggested that the SNP could alter the sequence recognized by the Neuron-Restrictive Silencer Factor (NRSF), whose deregulation has been associated with the development of several tumors. The mechanistic link between the allele and the disease has not been completely clarified yet but the epidemiologic evidences that link the DNA region to increased cancer risk are convincing. In conclusion, our results suggest rs2518719 as a pleiotropic CDKN2A variant associated with the risk of developing PNETs. © 2016 The Author(s).
Συγγραφείς:
Campa, D.
Capurso, G.
Pastore, M.
Talar-Wojnarowska, R.
Milanetto, A.C.
Landoni, L.
Maiello, E.
Lawlor, R.T.
Malecka-Panas, E.
Funel, N.
Gazouli, M.
De Bonis, A.
Klüter, H.
Rinzivillo, M.
Delle Fave, G.
Hackert, T.
Landi, S.
Bugert, P.
Bambi, F.
Archibugi, L.
Scarpa, A.
Katzke, V.
Dervenis, C.
Liço, V.
Furlanello, S.
Strobel, O.
Tavano, F.
Basso, D.
Kaaks, R.
Pasquali, C.
Gentiluomo, M.
Rizzato, C.
Canzian, F.
Λέξεις-κλειδιά:
CDKN2A protein, human; CDKN2B protein, human; cyclin dependent kinase inhibitor 2B; cyclin dependent kinase inhibitor 2C, aged; allele; biology; case control study; female; gene linkage disequilibrium; gene silencing; genetic association study; genetic predisposition; genetics; genotype; germline mutation; homozygote; human; male; middle aged; neuroendocrine tumor; odds ratio; pancreas tumor; risk; single nucleotide polymorphism; statistical model, Aged; Alleles; Case-Control Studies; Computational Biology; Cyclin-Dependent Kinase Inhibitor p15; Cyclin-Dependent Kinase Inhibitor p18; Female; Gene Silencing; Genetic Association Studies; Genetic Predisposition to Disease; Genotype; Germ-Line Mutation; Homozygote; Humans; Linkage Disequilibrium; Male; Middle Aged; Models, Statistical; Neuroendocrine Tumors; Odds Ratio; Pancreatic Neoplasms; Polymorphism, Single Nucleotide; Risk
