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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, Vol. 12, 2021, p. 693933.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Lu, Y, Corradi, C, Gentiluomo, M, López de Maturana, E, Theodoropoulos, GE, Roth, S, Maiello, E, Morelli, L, Archibugi, L, Izbicki, JR, Sarlós, P, Kiudelis, V, Oliverius, M, Aoki, MN, Vashist, Y, van Eijck, CHJ, Gazouli, M, Talar-Wojnarowska, R, Mambrini, A, Pezzilli, R, Bueno-de-Mesquita, B, Hegyi, P, Souček, P, Neoptolemos, JP, Di Franco, G, Sperti, C, Kauffmann, EF, Hlaváč, V, Uzunoğlu, FG, Ermini, S, Małecka-Panas, E, Lucchesi, M, Vanella, G, Dijk, F, Mohelníková-Duchoňová, B, Bambi, F, Petrone, MC, Jamroziak, K, Guo, F, Kolarova, K, Capretti, G, Milanetto, AC, Ginocchi, L, Loveček, M, Puzzono, M, van Laarhoven, HWM, Carrara, S, Ivanauskas, A, Papiris, K, Basso, D, Arcidiacono, PG, Izbéki, F, Chammas, R, Vodicka, P, Hackert, T, Pasquali, C, Piredda, ML, Costello-Goldring, E, Cavestro, GM, Szentesi, A, Tavano, F, Włodarczyk, B, Brenner, H, Kreivenaite, E, Gao, X, Bunduc, S, Vermeulen, RCH, Schneider, MA, Latiano, A, Gioffreda, D, Testoni, SGG, Kupcinskas, J, Lawlor, RT, Capurso, G, Malats, N, Campa, D & Canzian, F 2021, 'Association of Genetic Variants Affecting microRNAs and Pancreatic Cancer Risk', FRONT GENET, vol. 12, pp. 693933. https://doi.org/10.3389/fgene.2021.693933

APA

Lu, Y., Corradi, C., Gentiluomo, M., López de Maturana, E., Theodoropoulos, G. E., Roth, S., Maiello, E., Morelli, L., Archibugi, L., Izbicki, J. R., Sarlós, P., Kiudelis, V., Oliverius, M., Aoki, M. N., Vashist, Y., van Eijck, C. H. J., Gazouli, M., Talar-Wojnarowska, R., Mambrini, A., ... Canzian, F. (2021). Association of Genetic Variants Affecting microRNAs and Pancreatic Cancer Risk. FRONT GENET, 12, 693933. https://doi.org/10.3389/fgene.2021.693933

Vancouver

Lu Y, Corradi C, Gentiluomo M, López de Maturana E, Theodoropoulos GE, Roth S et al. Association of Genetic Variants Affecting microRNAs and Pancreatic Cancer Risk. FRONT GENET. 2021;12:693933. https://doi.org/10.3389/fgene.2021.693933

Bibtex

@article{fd99bec097154ea3ab8e12a88aee72b1,
title = "Association of Genetic Variants Affecting microRNAs and Pancreatic Cancer Risk",
abstract = "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.",
author = "Ye Lu and Chiara Corradi and Manuel Gentiluomo and {L{\'o}pez de Maturana}, Evangelina and Theodoropoulos, {George E} and Susanne Roth and Evaristo Maiello and Luca Morelli and Livia Archibugi and Izbicki, {Jakob R} and Patricia Sarl{\'o}s and Vytautas Kiudelis and Martin Oliverius and Aoki, {Mateus N{\'o}brega} and Yogesh Vashist and {van Eijck}, {Casper H J} and Maria Gazouli and Renata Talar-Wojnarowska and Andrea Mambrini and Raffaele Pezzilli and Bas Bueno-de-Mesquita and P{\'e}ter Hegyi and Pavel Sou{\v c}ek and Neoptolemos, {John P} and {Di Franco}, Gregorio and Cosimo Sperti and Kauffmann, {Emanuele F} and Viktor Hlav{\'a}{\v c} and Uzunoğlu, {Faik G} and Stefano Ermini and Ewa Ma{\l}ecka-Panas and Maurizio Lucchesi and Giuseppe Vanella and Frederike Dijk and Beatrice Moheln{\'i}kov{\'a}-Ducho{\v n}ov{\'a} and Franco Bambi and Petrone, {Maria Chiara} and Krzysztof Jamroziak and Feng Guo and Katerina Kolarova and Giovanni Capretti and Milanetto, {Anna Caterina} and Laura Ginocchi and Martin Love{\v c}ek and Marta Puzzono and {van Laarhoven}, {Hanneke W M} and Silvia Carrara and Audrius Ivanauskas and Konstantinos Papiris and Daniela Basso and Arcidiacono, {Paolo G} and Ferenc Izb{\'e}ki and Roger Chammas and Pavel Vodicka and Thilo Hackert and Claudio Pasquali and Piredda, {Maria L} and Eithne Costello-Goldring and Cavestro, {Giulia Martina} and Andrea Szentesi and Francesca Tavano and Barbara W{\l}odarczyk and Hermann Brenner and Edita Kreivenaite and Xin Gao and Stefania Bunduc and Vermeulen, {Roel C H} and Schneider, {Martin A} and Anna Latiano and Domenica Gioffreda and Testoni, {Sabrina G G} and Juozas Kupcinskas and Lawlor, {Rita T} and Gabriele Capurso and N{\'u}ria Malats and Daniele Campa and Federico Canzian",
note = "Copyright {\textcopyright} 2021 Lu, Corradi, Gentiluomo, L{\'o}pez de Maturana, Theodoropoulos, Roth, Maiello, Morelli, Archibugi, Izbicki, Sarl{\'o}s, Kiudelis, Oliverius, Aoki, Vashist, van Eijck, Gazouli, Talar-Wojnarowska, Mambrini, Pezzilli, Bueno-de-Mesquita, Hegyi, Sou{\v c}ek, Neoptolemos, Di Franco, Sperti, Kauffmann, Hlav{\'a}{\v c}, Uzunoğlu, Ermini, Ma{\l}ecka-Panas, Lucchesi, Vanella, Dijk, Moheln{\'i}kov{\'a}-Ducho{\v n}ov{\'a}, Bambi, Petrone, Jamroziak, Guo, Kolarova, Capretti, Milanetto, Ginocchi, Love{\v c}ek, Puzzono, van Laarhoven, Carrara, Ivanauskas, Papiris, Basso, Arcidiacono, Izb{\'e}ki, Chammas, Vodicka, Hackert, Pasquali, Piredda, Costello-Goldring, Cavestro, Szentesi, Tavano, W{\l}odarczyk, Brenner, Kreivenaite, Gao, Bunduc, Vermeulen, Schneider, Latiano, Gioffreda, Testoni, Kupcinskas, Lawlor, Capurso, Malats, Campa and Canzian.",
year = "2021",
doi = "10.3389/fgene.2021.693933",
language = "English",
volume = "12",
pages = "693933",
journal = "FRONT GENET",
issn = "1664-8021",
publisher = "Lausanne : Frontiers Research Foundation",

}

RIS

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 -