Genome-wide scan of long noncoding RNA single nucleotide polymorphisms and pancreatic cancer susceptibility

被引：30

作者：

Corradi, Chiara ^{[1
]}

Gentiluomo, Manuel ^{[1
]}

Gajdan, Laszlo ^{[2
]}

Cavestro, Giulia Martina ^{[3
]}

Kreivenaite, Edita ^{[4
,5
]}

Di Franco, Gregorio ^{[6
]}

Sperti, Cosimo ^{[7
]}

Giaccherini, Matteo ^{[1
]}

Petrone, Maria Chiara ^{[8
]}

Tavano, Francesca ^{[9
,10
,11
]}

Gioffreda, Domenica ^{[9
,10
,11
]}

Morelli, Luca ^{[6
]}

Soucek, Pavel ^{[12
]}

Andriulli, Angelo ^{[9
,10
,11
]}

Izbicki, Jakob R. ^{[13
]}

Napoli, Niccolo ^{[14
]}

Malecka-Panas, Ewa ^{[15
]}

Hegyi, Peter ^{[16
,17
]}

Neoptolemos, John P. ^{[18
]}

Landi, Stefano ^{[1
]}

Vashist, Yogesh ^{[13
]}

Pasquali, Claudio ^{[7
]}

Lu, Ye ^{[19
]}

Cervena, Klara ^{[20
,21
]}

Theodoropoulos, George E. ^{[22
]}

Moz, Stefania ^{[7
]}

Capurso, Gabriele ^{[8
,23
]}

Strobel, Oliver ^{[18
]}

Carrara, Silvia ^{[24
]}

Hackert, Thilo ^{[18
]}

Hlavac, Viktor ^{[12
]}

Archibugi, Livia ^{[8
,23
]}

Oliverius, Martin ^{[25
,26
]}

Vanella, Giuseppe ^{[8
,23
]}

Vodicka, Pavel ^{[20
,21
]}

Arcidiacono, Paolo Giorgio ^{[8
]}

Pezzilli, Raffaele ^{[27
]}

Milanetto, Anna Caterina ^{[7
]}

Lawlor, Rita T. ^{[28
]}

Ivanauskas, Audrius ^{[4
,5
]}

Szentesi, Andrea ^{[16
,17
]}

Kupcinskas, Juozas ^{[4
,5
]}

Testoni, Sabrina G. G. ^{[8
]}

Lovecek, Martin ^{[29
,30
]}

Nentwich, Michael ^{[13
]}

Gazouli, Maria ^{[31
]}

Luchini, Claudio ^{[32
]}

Zuppardo, Raffaella Alessia ^{[3
]}

Darvasi, Erika ^{[17
]}

Brenner, Hermann ^{[33
,34
,35
,36
]}

机构：

[1] Univ Pisa, Dept Biol, Via Derna 1, I-56126 Pisa, Italy

[2] Szent Gyorgy Univ Teaching Hosp Fejer Cty, Szekesfehervar, Hungary

[3] Univ Vita Salute San Raffaele, IRCCS Osped San Raffaele Sci Inst, Div Expt Oncol, Gastroenterol & Gastrointestinal Endoscopy Unit, Milan, Italy

[4] Lithuanian Univ Hlth Sci, Dept Gastroenterol, Kaunas, Lithuania

[5] Lithuanian Univ Hlth Sci, Inst Digest Res, Kaunas, Lithuania

[6] Univ Pisa, Dept Translat Res & New Technol Med & Surg, Gen Surg Unit, Pisa, Italy

[7] Univ Padua, Dept Surg Oncol & Gastroenterol DiSCOG, Padua, Italy

[8] Univ Vita Salute San Raffaele, Pancreas Translat & Clin Res Ctr, IRCCS San Raffaele Sci Inst, Pancreatobiliary Endoscopy & Endosonog Div, Milan, Italy

[9] IRCCS Sci Inst, Div Gastroenterol, San Giovanni Rotondo, Italy

[10] IRCCS Sci Inst, Res Lab, San Giovanni Rotondo, Italy

[11] Reg Gen Hosp Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy

[12] Charles Univ Prague, Fac Med Pilsen, Biomed Ctr, Plzen, Czech Republic

[13] Univ Med Ctr Hamburg Eppendorf, Dept Gen Visceral & Thorac Surg, Hamburg, Germany

[14] Univ Pisa, UO Chirurg Gen & Trapianti, Pisa, Italy

[15] Med Univ Lodz, Dept Digest Tract Dis, Lodz, Poland

[16] Univ Pecs, Med Sch, Inst Translat Med, Pecs, Hungary

[17] Univ Szeged, Dept Med 1, Szeged, Hungary

[18] Heidelberg Univ, Dept Gen Surg, Heidelberg, Germany

[19] German Canc Res Ctr, Genom Epidemiol Grp, Heidelberg, Germany

[20] First Med Fac, Inst Biol & Med Genet, Prague, Czech Republic

[21] Czech Acad Sci, Inst Expt Med, Prague, Czech Republic

[22] Natl & Kapodistrian Univ Athens, Athens Med Sch, Dept Propaedeut Surg 1, Colorectal Unit, Athens, Greece

[23] Sapienza Univ Rome, St Andrea Hosp, Fac Med & Psychol, Rome, Italy

[24] Humanitas Res Hosp, Div Gastroenterol, Digest Endoscopy Unit, Rozzano, Italy

[25] Charles Univ Prague, Fac Hosp Kralovske Vinohrady, Dept Surg, Prague, Czech Republic

[26] Charles Univ Prague, Fac Med 3, Prague, Czech Republic

[27] San Carlo Hosp, Gastroenterol, Potenza, Italy

[28] Univ & Hosp Trust Verona, ARC NET Ctr Appl Res Canc, Verona, Italy

[29] Palacky Univ Olomouc, Fac Med & Dent, Dept Surg 1, Olomouc, Czech Republic

[30] Univ Hosp Olomouc, Olomouc, Czech Republic

[31] Natl & Kapodistrian Univ Athens, Med Sch, Dept Basic Med Sci, Lab Biol, Athens, Greece

[32] Univ Verona, Dept Diagnost & Publ Hlth, Sect Pathol, Verona, Italy

[33] German Canc Res Ctr, Div Clin Epidemiol & Aging Res, Heidelberg, Germany

[34] German Canc Res Ctr, Div Prevent Oncol, Heidelberg, Germany

[35] Natl Ctr Tumor Dis NCT, Heidelberg, Germany

[36] German Canc Res Ctr, German Canc Consortium DKTK, Heidelberg, Germany

[37] Fundeni Clin Inst, Ctr Gastroenterol, Bucharest, Romania

[38] Inst Hematol & Transfus Med, Dept Hematol, Warsaw, Poland

来源：

INTERNATIONAL JOURNAL OF CANCER | 2021年 / 148卷 / 11期

关键词：

association study; long noncoding RNA; pancreatic cancer; single nucleotide polymorphism; GENETIC-VARIANTS; RISK-FACTORS; ASSOCIATION; LOCI; LIVER;

D O I：

10.1002/ijc.33475

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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 x 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.

引用

页码：2779 / 2788

页数：10

共 51 条

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← 1 2 3 4 5 6 →

共 51 条

[1] Genome-wide association study identifies variants in the ABO locus associated with susceptibility to pancreatic cancer
Amundadottir, Laufey
Kraft, Peter
Stolzenberg-Solomon, Rachael Z.
Fuchs, Charles S.
Petersen, Gloria M.
Arslan, Alan A.
Bueno-de-Mesquita, H. Bas
Gross, Myron
Helzlsouer, Kathy
Jacobs, Eric J.
LaCroix, Andrea
Zheng, Wei
Albanes, Demetrius
Bamlet, William
Berg, Christine D.
Berrino, Franco
Bingham, Sheila
Buring, Julie E.
Bracci, Paige M.
Canzian, Federico
Clavel-Chapelon, Francoise
Clipp, Sandra
Cotterchio, Michelle
de Andrade, Mariza
Duell, Eric J.
Fox, John W., Jr.
Gallinger, Steven
Gaziano, J. Michael
Giovannucci, Edward L.
Goggins, Michael
Gonzalez, Carlos A.
Hallmans, Goran
Hankinson, Susan E.
Hassan, Manal
Holly, Elizabeth A.
Hunter, David J.
Hutchinson, Amy
Jackson, Rebecca
Jacobs, Kevin B.
Jenab, Mazda
Kaaks, Rudolf
Klein, Alison P.
Kooperberg, Charles
Kurtz, Robert C.
Li, Donghui
Lynch, Shannon M.
Mandelson, Margaret
McWilliams, Robert R.
Mendelsohn, Julie B.
Michaud, Dominique S.
[J]. NATURE GENETICS, 2009, 41 (09) : 986 - U47
[2] DAAM1 Is a Formin Required for Centrosome Re-Orientation during Cell Migration
Ang, Su-Fen
Zhao, Zhuo-shen
Lim, Louis
Manser, Ed
[J]. PLOS ONE, 2010, 5 (09):
[3] Pancreatic cancer genomes reveal aberrations in axon guidance pathway genes
Biankin, Andrew V.
Waddell, Nicola
Kassahn, Karin S.
Gingras, Marie-Claude
Muthuswamy, Lakshmi B.
Johns, Amber L.
Miller, David K.
Wilson, Peter J.
Patch, Ann-Marie
Wu, Jianmin
Chang, David K.
Cowley, Mark J.
Gardiner, Brooke B.
Song, Sarah
Harliwong, Ivon
Idrisoglu, Senel
Nourse, Craig
Nourbakhsh, Ehsan
Manning, Suzanne
Wani, Shivangi
Gongora, Milena
Pajic, Marina
Scarlett, Christopher J.
Gill, Anthony J.
Pinho, Andreia V.
Rooman, Ilse
Anderson, Matthew
Holmes, Oliver
Leonard, Conrad
Taylor, Darrin
Wood, Scott
Xu, Qinying
Nones, Katia
Fink, J. Lynn
Christ, Angelika
Bruxner, Tim
Cloonan, Nicole
Kolle, Gabriel
Newell, Felicity
Pinese, Mark
Mead, R. Scott
Humphris, Jeremy L.
Kaplan, Warren
Jones, Marc D.
Colvin, Emily K.
Nagrial, Adnan M.
Humphrey, Emily S.
Chou, Angela
Chin, Venessa T.
Chantrill, Lorraine A.
[J]. NATURE, 2012, 491 (7424) : 399 - 405
[4] Common germline variants within the CDKN2A/2B region affect risk of pancreatic neuroendocrine tumors
Campa, Daniele
Capurso, Gabriele
Pastore, Manuela
Talar-Wojnarowska, Renata
Milanetto, Anna Caterina
Landoni, Luca
Maiello, Evaristo
Lawlor, Rita T.
Malecka-Panas, Ewa
Funel, Niccola
Gazouli, Maria
De Bonis, Antonio
Klueter, Harald
Rinzivillo, Maria
Delle Fave, Gianfranco
Hackert, Thilo
Landi, Stefano
Bugert, Peter
Bambi, Franco
Archibugi, Livia
Scarpa, Aldo
Katzke, Verena
Dervenis, Christos
Lico, Valbona
Furlanello, Sara
Strobel, Oliver
Tavano, Francesca
Basso, Daniela
Kaaks, Rudolf
Pasquali, Claudio
Gentiluomo, Manuel
Rizzato, Cosmeri
Canzian, Federico
[J]. SCIENTIFIC REPORTS, 2016, 6
[5] Functional single nucleotide polymorphisms within the cyclin-dependent kinase inhibitor 2A/2B region affect pancreatic cancer risk
Campa, Daniele
Pastore, Manuela
Gentiluomo, Manuel
Talar-Wojnarowska, Renata
Kupcinskas, Juozas
Malecka-Panas, Ewa
Neoptolemos, John P.
Niesen, Willem
Vodicka, Pavel
Delle Fave, Gianfranco
Bueno-de-Mesquita, H. Bas
Gazouli, Maria
Pacetti, Paola
Di Leo, Milena
Ito, Hidemi
Klueter, Harald
Soucek, Pavel
Corbo, Vincenzo
Yamao, Kenji
Hosono, Satoyo
Kaaks, Rudolf
Vashist, Yogesh
Gioffreda, Domenica
Strobel, Oliver
Shimizu, Yasuhiro
Dijk, Frederike
Andriulli, Angelo
Ivanauskas, Audrius
Bugert, Peter
Tavano, Francesca
Vodickova, Ludmila
Zambon, Carlo Federico
Lovecek, Martin
Landi, Stefano
Key, Timothy J.
Boggi, Ugo
Pezzilli, Raffaele
Jamroziak, Krzysztof
Mohelnikova-Duchonova, Beatrice
Mambrini, Andrea
Bambi, Franco
Busch, Olivier
Pazienza, Valerio
Valente, Roberto
Theodoropoulos, George E.
Hackert, Thilo
Capurso, Gabriele
Cavestro, Giulia Martina
Pasquali, Claudio
Basso, Daniela
[J]. ONCOTARGET, 2016, 7 (35) : 57011 - 57020
[6] TERT gene harbors multiple variants associated with pancreatic cancer susceptibility
Campa, Daniele
Rizzato, Cosmeri
Stolzenberg-Solomon, Rachael
Pacetti, Paola
Vodicka, Pavel
Cleary, Sean P.
Capurso, Gabriele
Bueno-de-Mesquita, H. B
Werner, Jens
Gazouli, Maria
Butterbach, Katja
Ivanauskas, Audrius
Giese, Nathalia
Petersen, Gloria M.
Fogar, Paola
Wang, Zhaoming
Bassi, Claudio
Ryska, Miroslav
Theodoropoulos, George E.
Kooperberg, Charles
Li, Donghui
Greenhalf, William
Pasquali, Claudio
Hackert, Thilo
Fuchs, Charles S.
Mohelnikova-Duchonova, Beatrice
Sperti, Cosimo
Funel, Niccola
Dieffenbach, Aida Karina
Wareham, Nicholas J.
Buring, Julie
Holcatova, Ivana
Costello, Eithne
Zambon, Carlo-Federico
Kupcinskas, Juozas
Risch, Harvey A.
Kraft, Peter
Bracci, Paige M.
Pezzilli, Raffaele
Olson, Sara H.
Sesso, Howard D.
Hartge, Patricia
Strobel, Oliver
Malecka-Panas, Ewa
Visvanathan, Kala
Arslan, Alan A.
Pedrazzoli, Sergio
Soucek, Pavel
Gioffreda, Domenica
Key, Timothy J.
[J]. INTERNATIONAL JOURNAL OF CANCER, 2015, 137 (09) : 2175 - 2183
[7] Lack of Replication of Seven Pancreatic Cancer Susceptibility Loci Identified in Two Asian Populations
Campa, Daniele
Rizzato, Cosmeri
Bauer, Andrea S.
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