Common germline variants within the CDKN2A/2B region affect risk of pancreatic neuroendocrine tumors

Daniele Campa, Gabriele Capurso, Manuela Pastore, Renata Talar-Wojnarowska, Anna Caterina Milanetto, Luca Landoni, Evaristo Maiello, Rita T. Lawlor, Ewa Malecka-Panas, Niccola Funel, Maria Gazouli, Antonio De Bonis, Harald Klüter, Maria Rinzivillo, Gianfranco Delle Fave, Thilo Hackert, Stefano Landi, Peter Bugert, Franco Bambi, Livia ArchibugiAldo Scarpa, Verena A. Katzke, Christos Dervenis, Valbona Liço, Sara Furlanello, Oliver Strobel, Francesca Tavano, Daniela Basso, Rudolf Kaaks, Claudio Pasquali, Manuel Gentiluomo, Cosmeri Rizzato, Federico Canzian

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)39565
JournalScientific Reports
Publication statusPublished - Dec 23 2016


  • Journal Article


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