Association between a polymorphic variant in the CDKN2B-AS1/ANRIL gene and pancreatic cancer risk.
Matteo Giaccherini, Riccardo Farinella, Manuel Gentiluomo, Beatrice Mohelnikova-Duchonova, Emanuele Federico Kauffmann, Matteo Palmeri, Faik Uzunoglu, Pavel Soucek, Dalius Petrauskas, Giulia Martina Cavestro, Romanas Zykus, Silvia Carrara, Raffaele Pezzilli, Marta Puzzono, Andrea Szentesi, John Neoptolemos, Livia Archibugi, Orazio Palmieri, Anna Caterina Milanetto, Gabriele Capurso, Casper H J van Eijck, Hannah Stocker, Rita T Lawlor, Pavel Vodicka, Martin Lovecek, Jakob R Izbicki, Francesco Perri, Rita Kupcinskaite-Noreikiene, Mara Götz, Juozas Kupcinskas, Tamás Hussein, Péter Hegyi, Olivier R Busch, Thilo Hackert, Andrea Mambrini, Hermann Brenner, Maurizio Lucchesi, Daniela Basso, Francesca Tavano, Ben Schöttker, Giuseppe Vanella, Stefania Bunduc, Ágota Petrányi, Stefano Landi, Luca Morelli, Federico Canzian, Daniele Campa
International journal of cancer 2023 Jul 15Genes carrying high-penetrance germline mutations may also be associated with cancer susceptibility through common low-penetrance genetic variants. To increase the knowledge on genetic pancreatic ductal adenocarcinoma (PDAC) aetiology, the common genetic variability of PDAC familial genes was analysed in our study. We conducted a multiphase study analysing 7745 single nucleotide polymorphisms (SNPs) from 29 genes reported to harbour a high-penetrance PDAC-associated mutation in at least one published study. To assess the effect of the SNPs on PDAC risk, a total of 14 666 PDAC cases and 221 897 controls across five different studies were analysed. The T allele of the rs1412832 polymorphism, that is situated in the CDKN2B-AS1/ANRIL, showed a genome-wide significant association with increased risk of developing PDAC (OR = 1.11, 95% CI = 1.07-1.15, P = 5.25 × 10-9 ). CDKN2B-AS1/ANRIL is a long noncoding RNA, situated in 9p21.3, and regulates many target genes, among which CDKN2A (p16) that frequently shows deleterious somatic and germline mutations and deregulation in PDAC. Our results strongly support the role of the genetic variability of the 9p21.3 region in PDAC aetiopathogenesis and highlight the importance of secondary analysis as a tool for discovering new risk loci in complex human diseases. © 2022 UICC.
Citation
Matteo Giaccherini, Riccardo Farinella, Manuel Gentiluomo, Beatrice Mohelnikova-Duchonova, Emanuele Federico Kauffmann, Matteo Palmeri, Faik Uzunoglu, Pavel Soucek, Dalius Petrauskas, Giulia Martina Cavestro, Romanas Zykus, Silvia Carrara, Raffaele Pezzilli, Marta Puzzono, Andrea Szentesi, John Neoptolemos, Livia Archibugi, Orazio Palmieri, Anna Caterina Milanetto, Gabriele Capurso, Casper H J van Eijck, Hannah Stocker, Rita T Lawlor, Pavel Vodicka, Martin Lovecek, Jakob R Izbicki, Francesco Perri, Rita Kupcinskaite-Noreikiene, Mara Götz, Juozas Kupcinskas, Tamás Hussein, Péter Hegyi, Olivier R Busch, Thilo Hackert, Andrea Mambrini, Hermann Brenner, Maurizio Lucchesi, Daniela Basso, Francesca Tavano, Ben Schöttker, Giuseppe Vanella, Stefania Bunduc, Ágota Petrányi, Stefano Landi, Luca Morelli, Federico Canzian, Daniele Campa. Association between a polymorphic variant in the CDKN2B-AS1/ANRIL gene and pancreatic cancer risk. International journal of cancer. 2023 Jul 15;153(2):373-379
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PMID: 36451333
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