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Genome‐wide scan of long noncoding RNA single nucleotide polymorphism s and pancreatic cancer susceptibility
Author(s) -
Corradi Chiara,
Gentiluomo Manuel,
Gajdán László,
Cavestro Giulia Martina,
Kreivenaite Edita,
Di Franco Gregorio,
Sperti Cosimo,
Giaccherini Matteo,
Petrone Maria Chiara,
Tavano Francesca,
Gioffreda Domenica,
Morelli Luca,
Soucek Pavel,
Andriulli Angelo,
Izbicki Jakob R.,
Napoli Niccolò,
MałeckaPanas Ewa,
Hegyi Péter,
Neoptolemos John P.,
Landi Stefano,
Vashist Yogesh,
Pasquali Claudio,
Lu Ye,
Cervena Klara,
Theodoropoulos George E.,
Moz Stefania,
Capurso Gabriele,
Strobel Oliver,
Carrara Silvia,
Hackert Thilo,
Hlavac Viktor,
Archibugi Livia,
Oliverius Martin,
Vanella Giuseppe,
Vodicka Pavel,
Arcidiacono Paolo Giorgio,
Pezzilli Raffaele,
Milanetto Anna Caterina,
Lawlor Rita T.,
Ivanauskas Audrius,
Szentesi Andrea,
Kupcinskas Juozas,
Testoni Sabrina G. G.,
Lovecek Martin,
Nentwich Michael,
Gazouli Maria,
Luchini Claudio,
Zuppardo Raffaella Alessia,
Darvasi Erika,
Brenner Hermann,
Gheorghe Cristian,
Jamroziak Krzysztof,
Canzian Federico,
Campa Daniele
Publication year - 2021
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.33475
Subject(s) - biology , genetics , single nucleotide polymorphism , microrna , long non coding rna , gene , genome , genome wide association study , snp , locus (genetics) , genetic association , allele , computational biology , rna , genotype
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.