Περίληψη:
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. © 2021 UICC
Συγγραφείς:
Corradi, C.
Gentiluomo, M.
Gajdán, L.
Cavestro, G.M.
Kreivenaite, E.
Di Franco, G.
Sperti, C.
Giaccherini, M.
Petrone, M.C.
Tavano, F.
Gioffreda, D.
Morelli, L.
Soucek, P.
Andriulli, A.
Izbicki, J.R.
Napoli, N.
Małecka-Panas, E.
Hegyi, P.
Neoptolemos, J.P.
Landi, S.
Vashist, Y.
Pasquali, C.
Lu, Y.
Cervena, K.
Theodoropoulos, G.E.
Moz, S.
Capurso, G.
Strobel, O.
Carrara, S.
Hackert, T.
Hlavac, V.
Archibugi, L.
Oliverius, M.
Vanella, G.
Vodicka, P.
Arcidiacono, P.G.
Pezzilli, R.
Milanetto, A.C.
Lawlor, R.T.
Ivanauskas, A.
Szentesi, A.
Kupcinskas, J.
Testoni, S.G.G.
Lovecek, M.
Nentwich, M.
Gazouli, M.
Luchini, C.
Zuppardo, R.A.
Darvasi, E.
Brenner, H.
Gheorghe, C.
Jamroziak, K.
Canzian, F.
Campa, D.
Λέξεις-κλειδιά:
cyclin dependent kinase inhibitor 2B; hsa mir 1256; long untranslated RNA; microRNA; unclassified drug; CDKN2B protein, human; cyclin dependent kinase inhibitor 2B; long untranslated RNA; microRNA; MIRN1256 microRNA, human, adult; aged; Article; CDKN2B gene; controlled study; female; gene; genetic association; genetic risk; genetic susceptibility; genetic variability; genome-wide association study; human; lnc SMC2 1 gene; major clinical study; male; pancreas adenocarcinoma; priority journal; RNA binding; single nucleotide polymorphism; biology; case control study; genetic predisposition; genetics; genome-wide association study; middle aged; pancreas carcinoma; pancreas tumor; procedures, Aged; Carcinoma, Pancreatic Ductal; Case-Control Studies; Computational Biology; Cyclin-Dependent Kinase Inhibitor p15; Female; Genetic Predisposition to Disease; Genome-Wide Association Study; Humans; Male; MicroRNAs; Middle Aged; Pancreatic Neoplasms; Polymorphism, Single Nucleotide; RNA, Long Noncoding
