Genome‐wide scan of long noncoding <scp>RNA</scp> single nucleotide polymorphism<scp>s</scp> and pancreatic cancer susceptibility
Chiara Corradi, Manuel Gentiluomo, László Gajdán, Giulia Martina Cavestro, Edita Kreivėnaitė, Gregorio Di Franco, Cosimo Sperti, Matteo Giaccherini, Maria Chiara Petrone, Francesca Tavano, Domenica Gioffreda, Luca Morelli, Pavel Souček, Angelo Andriulli, Jakob R. Izbicki, Niccolò Napoli, Ewa Małecka‐Panas, Péter Hegyi, John P. Neoptolemos, Stefano Landi, Yogesh K. Vashist, Claudio Pasquali, Ye Lu, Klára Červená, George Theodoropoulos, Stefania Moz, Gabriele Capurso, Oliver Strobel, Silvia Carrara, Thilo Hackert, Viktor Hlaváč, Lívia Archibugi, Martin Oliverius, Giuseppe Vanella, Pavel Vodička, Paolo Giorgio Arcidiacono, Raffaele Pezzilli, Anna Caterina Milanetto, Rita T. Lawlor, Audrius Ivanauskas, Andrea Szentesi, Juozas Kupčinskas, Sabrina Gloria Giulia Testoni, Martin Loveček, Michael F. Nentwich, Maria Gazouli, Claudio Luchini, Raffaella Alessia Zuppardo, Erika Darvasi, Hermann Brenner, Cristian Gheorghe, Krzysztof Jamroziak, Federico Canzian, Daniele Campa
Abstract
Abstract Pancreatic ductal adenocarcinoma (PDAC) is projected to become the second cancer‐related cause of death by 2030. Identifying novel risk factors, including genetic risk loci, could be instrumental in risk stratification and implementation of prevention strategies. Long noncoding RNAs (lncRNAs) are involved in regulation of key biological processes, and the possible role of their genetic variability has been unexplored so far. Combining genome wide association studies and functional data, we investigated the genetic variability in all lncRNAs. We analyzed 9893 PDAC cases and 9969 controls and identified a genome‐wide significant association between the rs7046076 SNP and risk of developing PDAC ( P = 9.73 × 10 −9 ). This SNP is located in the NONHSAG053086.2 ( lnc‐SMC2‐1 ) gene and the risk allele is predicted to disrupt the binding of the lncRNA with the micro‐RNA (miRNA) hsa‐mir‐1256 that regulates several genes involved in cell cycle, such as CDKN2B . The CDKN2B region is pleiotropic and its genetic variants have been associated with several human diseases, possibly though an imperfect interaction between lncRNA and miRNA. We present a novel PDAC risk locus, supported by a genome‐wide statistical significance and a plausible biological mechanism.