Association of Genetic Variants Affecting microRNAs and Pancreatic Cancer Risk
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Association of Genetic Variants Affecting microRNAs and Pancreatic Cancer Risk. / Lu, Ye; Corradi, Chiara; Gentiluomo, Manuel; López de Maturana, Evangelina; Theodoropoulos, George E; Roth, Susanne; Maiello, Evaristo; Morelli, Luca; Archibugi, Livia; Izbicki, Jakob R; Sarlós, Patricia; Kiudelis, Vytautas; Oliverius, Martin; Aoki, Mateus Nóbrega; Vashist, Yogesh; van Eijck, Casper H J; Gazouli, Maria; Talar-Wojnarowska, Renata; Mambrini, Andrea; Pezzilli, Raffaele; Bueno-de-Mesquita, Bas; Hegyi, Péter; Souček, Pavel; Neoptolemos, John P; Di Franco, Gregorio; Sperti, Cosimo; Kauffmann, Emanuele F; Hlaváč, Viktor; Uzunoğlu, Faik G; Ermini, Stefano; Małecka-Panas, Ewa; Lucchesi, Maurizio; Vanella, Giuseppe; Dijk, Frederike; Mohelníková-Duchoňová, Beatrice; Bambi, Franco; Petrone, Maria Chiara; Jamroziak, Krzysztof; Guo, Feng; Kolarova, Katerina; Capretti, Giovanni; Milanetto, Anna Caterina; Ginocchi, Laura; Loveček, Martin; Puzzono, Marta; van Laarhoven, Hanneke W M; Carrara, Silvia; Ivanauskas, Audrius; Papiris, Konstantinos; Basso, Daniela; Arcidiacono, Paolo G; Izbéki, Ferenc; Chammas, Roger; Vodicka, Pavel; Hackert, Thilo; Pasquali, Claudio; Piredda, Maria L; Costello-Goldring, Eithne; Cavestro, Giulia Martina; Szentesi, Andrea; Tavano, Francesca; Włodarczyk, Barbara; Brenner, Hermann; Kreivenaite, Edita; Gao, Xin; Bunduc, Stefania; Vermeulen, Roel C H; Schneider, Martin A; Latiano, Anna; Gioffreda, Domenica; Testoni, Sabrina G G; Kupcinskas, Juozas; Lawlor, Rita T; Capurso, Gabriele; Malats, Núria; Campa, Daniele; Canzian, Federico.
in: FRONT GENET, Jahrgang 12, 2021, S. 693933.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Association of Genetic Variants Affecting microRNAs and Pancreatic Cancer Risk
AU - Lu, Ye
AU - Corradi, Chiara
AU - Gentiluomo, Manuel
AU - López de Maturana, Evangelina
AU - Theodoropoulos, George E
AU - Roth, Susanne
AU - Maiello, Evaristo
AU - Morelli, Luca
AU - Archibugi, Livia
AU - Izbicki, Jakob R
AU - Sarlós, Patricia
AU - Kiudelis, Vytautas
AU - Oliverius, Martin
AU - Aoki, Mateus Nóbrega
AU - Vashist, Yogesh
AU - van Eijck, Casper H J
AU - Gazouli, Maria
AU - Talar-Wojnarowska, Renata
AU - Mambrini, Andrea
AU - Pezzilli, Raffaele
AU - Bueno-de-Mesquita, Bas
AU - Hegyi, Péter
AU - Souček, Pavel
AU - Neoptolemos, John P
AU - Di Franco, Gregorio
AU - Sperti, Cosimo
AU - Kauffmann, Emanuele F
AU - Hlaváč, Viktor
AU - Uzunoğlu, Faik G
AU - Ermini, Stefano
AU - Małecka-Panas, Ewa
AU - Lucchesi, Maurizio
AU - Vanella, Giuseppe
AU - Dijk, Frederike
AU - Mohelníková-Duchoňová, Beatrice
AU - Bambi, Franco
AU - Petrone, Maria Chiara
AU - Jamroziak, Krzysztof
AU - Guo, Feng
AU - Kolarova, Katerina
AU - Capretti, Giovanni
AU - Milanetto, Anna Caterina
AU - Ginocchi, Laura
AU - Loveček, Martin
AU - Puzzono, Marta
AU - van Laarhoven, Hanneke W M
AU - Carrara, Silvia
AU - Ivanauskas, Audrius
AU - Papiris, Konstantinos
AU - Basso, Daniela
AU - Arcidiacono, Paolo G
AU - Izbéki, Ferenc
AU - Chammas, Roger
AU - Vodicka, Pavel
AU - Hackert, Thilo
AU - Pasquali, Claudio
AU - Piredda, Maria L
AU - Costello-Goldring, Eithne
AU - Cavestro, Giulia Martina
AU - Szentesi, Andrea
AU - Tavano, Francesca
AU - Włodarczyk, Barbara
AU - Brenner, Hermann
AU - Kreivenaite, Edita
AU - Gao, Xin
AU - Bunduc, Stefania
AU - Vermeulen, Roel C H
AU - Schneider, Martin A
AU - Latiano, Anna
AU - Gioffreda, Domenica
AU - Testoni, Sabrina G G
AU - Kupcinskas, Juozas
AU - Lawlor, Rita T
AU - Capurso, Gabriele
AU - Malats, Núria
AU - Campa, Daniele
AU - Canzian, Federico
N1 - Copyright © 2021 Lu, Corradi, Gentiluomo, López de Maturana, Theodoropoulos, Roth, Maiello, Morelli, Archibugi, Izbicki, Sarlós, Kiudelis, Oliverius, Aoki, Vashist, van Eijck, Gazouli, Talar-Wojnarowska, Mambrini, Pezzilli, Bueno-de-Mesquita, Hegyi, Souček, Neoptolemos, Di Franco, Sperti, Kauffmann, Hlaváč, Uzunoğlu, Ermini, Małecka-Panas, Lucchesi, Vanella, Dijk, Mohelníková-Duchoňová, Bambi, Petrone, Jamroziak, Guo, Kolarova, Capretti, Milanetto, Ginocchi, Loveček, Puzzono, van Laarhoven, Carrara, Ivanauskas, Papiris, Basso, Arcidiacono, Izbéki, Chammas, Vodicka, Hackert, Pasquali, Piredda, Costello-Goldring, Cavestro, Szentesi, Tavano, Włodarczyk, Brenner, Kreivenaite, Gao, Bunduc, Vermeulen, Schneider, Latiano, Gioffreda, Testoni, Kupcinskas, Lawlor, Capurso, Malats, Campa and Canzian.
PY - 2021
Y1 - 2021
N2 - Genetic factors play an important role in the susceptibility to pancreatic cancer (PC). However, established loci explain a small proportion of genetic heritability for PC; therefore, more progress is needed to find the missing ones. We aimed at identifying single nucleotide polymorphisms (SNPs) affecting PC risk through effects on micro-RNA (miRNA) function. We searched in silico the genome for SNPs in miRNA seed sequences or 3 prime untranslated regions (3'UTRs) of miRNA target genes. Genome-wide association data of PC cases and controls from the Pancreatic Cancer Cohort (PanScan) Consortium and the Pancreatic Cancer Case-Control (PanC4) Consortium were re-analyzed for discovery, and genotyping data from two additional consortia (PanGenEU and PANDoRA) were used for replication, for a total of 14,062 cases and 11,261 controls. None of the SNPs reached genome-wide significance in the meta-analysis, but for three of them the associations were in the same direction in all the study populations and showed lower value of p in the meta-analyses than in the discovery phase. Specifically, rs7985480 was consistently associated with PC risk (OR = 1.12, 95% CI 1.07-1.17, p = 3.03 × 10-6 in the meta-analysis). This SNP is in linkage disequilibrium (LD) with rs2274048, which modulates binding of various miRNAs to the 3'UTR of UCHL3, a gene involved in PC progression. In conclusion, our results expand the knowledge of the genetic PC risk through miRNA-related SNPs and show the usefulness of functional prioritization to identify genetic polymorphisms associated with PC risk.
AB - Genetic factors play an important role in the susceptibility to pancreatic cancer (PC). However, established loci explain a small proportion of genetic heritability for PC; therefore, more progress is needed to find the missing ones. We aimed at identifying single nucleotide polymorphisms (SNPs) affecting PC risk through effects on micro-RNA (miRNA) function. We searched in silico the genome for SNPs in miRNA seed sequences or 3 prime untranslated regions (3'UTRs) of miRNA target genes. Genome-wide association data of PC cases and controls from the Pancreatic Cancer Cohort (PanScan) Consortium and the Pancreatic Cancer Case-Control (PanC4) Consortium were re-analyzed for discovery, and genotyping data from two additional consortia (PanGenEU and PANDoRA) were used for replication, for a total of 14,062 cases and 11,261 controls. None of the SNPs reached genome-wide significance in the meta-analysis, but for three of them the associations were in the same direction in all the study populations and showed lower value of p in the meta-analyses than in the discovery phase. Specifically, rs7985480 was consistently associated with PC risk (OR = 1.12, 95% CI 1.07-1.17, p = 3.03 × 10-6 in the meta-analysis). This SNP is in linkage disequilibrium (LD) with rs2274048, which modulates binding of various miRNAs to the 3'UTR of UCHL3, a gene involved in PC progression. In conclusion, our results expand the knowledge of the genetic PC risk through miRNA-related SNPs and show the usefulness of functional prioritization to identify genetic polymorphisms associated with PC risk.
U2 - 10.3389/fgene.2021.693933
DO - 10.3389/fgene.2021.693933
M3 - SCORING: Journal article
C2 - 34527018
VL - 12
SP - 693933
JO - FRONT GENET
JF - FRONT GENET
SN - 1664-8021
ER -