Common genetic variants associated with pancreatic adenocarcinoma may also modify risk of pancreatic neuroendocrine neoplasms

Ofure Obazee, Gabriele Capurso, Francesca Tavano, Livia Archibugi, Antonio De Bonis, William Greenhalf, Tim Key, Claudio Pasquali, Anna Caterina Milanetto, Thilo Hackert, Paola Fogar, Valbona Liço, Christos Dervenis, Rita T. Lawlor, Luca Landoni, Maria Gazouli, Carlo Federico Zambon, Niccola Funel, Oliver Strobel, Krzysztof JamroziakCinzia Cantù, Ewa Malecka-Panas, Stefano Landi, John P. Neoptolemos, Daniela Basso, Renata Talar-Wojnarowska, Maria Rinzivillo, Angelo Andriulli, Federico Canzian, Daniele Campa

Research output: Contribution to journalArticle

Abstract

Pancreatic neuroendocrine neoplasms (pNEN) account for less than 5% of all pancreatic neoplasms and genetic association studies on susceptibility to the disease are limited. We sought to identify possible overlap of genetic susceptibility loci between pancreatic ductal adenocarcinoma (PDAC) and pNEN; therefore, PDAC susceptibility variants (n = 23) from Caucasian genome-wide association studies (GWAS) were genotyped in 369 pNEN cases and 3277 controls from the PANcreatic Disease ReseArch (PANDoRA) consortium to evaluate the odds associated with pNEN risk, disease onset and tumor characteristics. Main effect analyses showed four PDAC susceptibility variants-rs9854771, rs1561927, rs9543325 and rs10919791 to be associated with pNEN risk. Subsequently, only associations with rs9543325, rs10919791 and rs1561927 were noteworthy with false positive report probability (FPRP) tests. Stratified analyses considering age at onset (50-year threshold), showed rs2736098, rs16986825 and rs9854771 to be associated with risk of developing pNEN at a younger age. Stratified analyses also showed some single nucleotide polymorphisms to be associated with different degrees of tumor grade, metastatic potential and functionality. Our results identify known GWAS PDAC susceptibility loci, which may also be involved in sporadic pNEN etiology and suggest that some genetic mechanisms governing pathogenesis of these two entities may be similar, with few of these loci being more influential in younger cases or tumor subtypes.

Original languageEnglish
Pages (from-to)360-367
Number of pages8
JournalCarcinogenesis
Volume39
Issue number3
DOIs
Publication statusPublished - Mar 8 2018

ASJC Scopus subject areas

  • Cancer Research

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    Obazee, O., Capurso, G., Tavano, F., Archibugi, L., Bonis, A. D., Greenhalf, W., Key, T., Pasquali, C., Milanetto, A. C., Hackert, T., Fogar, P., Liço, V., Dervenis, C., Lawlor, R. T., Landoni, L., Gazouli, M., Zambon, C. F., Funel, N., Strobel, O., ... Campa, D. (2018). Common genetic variants associated with pancreatic adenocarcinoma may also modify risk of pancreatic neuroendocrine neoplasms. Carcinogenesis, 39(3), 360-367. https://doi.org/10.1093/carcin/bgx150