Association between a polymorphic variant in the CDKN2B-AS1/ANRIL gene and pancreatic cancer risk

被引：16

作者：

Giaccherini, Matteo ^{[1
]}

Farinella, Riccardo ^{[1
]}

Gentiluomo, Manuel ^{[1
]}

Mohelnikova-Duchonova, Beatrice ^{[2
]}

Kauffmann, Emanuele Federico ^{[3
]}

Palmeri, Matteo ^{[4
]}

Uzunoglu, Faik ^{[5
]}

Soucek, Pavel ^{[6
]}

Petrauskas, Dalius ^{[7
]}

Cavestro, Giulia Martina ^{[8
]}

Zykus, Romanas ^{[7
]}

Carrara, Silvia ^{[9
]}

Pezzilli, Raffaele ^{[10
]}

Puzzono, Marta ^{[8
]}

Szentesi, Andrea ^{[11
,12
,13
]}

Neoptolemos, John ^{[14
]}

Archibugi, Livia ^{[15
,16
]}

Palmieri, Orazio ^{[17
]}

Milanetto, Anna Caterina ^{[18
]}

Capurso, Gabriele ^{[15
,16
]}

van Eijck, Casper H. J. ^{[19
]}

Stocker, Hannah ^{[20
]}

Lawlor, Rita T. ^{[21
]}

Vodicka, Pavel ^{[22
,23
,24
]}

Lovecek, Martin ^{[25
]}

Izbicki, Jakob R. ^{[5
]}

Perri, Francesco ^{[17
]}

Kupcinskaite-Noreikiene, Rita ^{[7
]}

Gotz, Mara ^{[5
]}

Kupcinskas, Juozas ^{[7
]}

Hussein, Tamas ^{[26
,27
]}

Hegyi, Peter ^{[11
,12
,26
,27
]}

Busch, Olivier R. ^{[28
]}

Hackert, Thilo ^{[14
]}

Mambrini, Andrea ^{[29
]}

Brenner, Hermann ^{[20
]}

Lucchesi, Maurizio ^{[29
]}

Basso, Daniela ^{[30
]}

Tavano, Francesca ^{[17
]}

Schottker, Ben ^{[20
]}

Vanella, Giuseppe ^{[15
,16
]}

Bunduc, Stefania ^{[26
,27
,31
]}

Petranyi, Agota ^{[27
,32
]}

Landi, Stefano ^{[1
]}

Morelli, Luca ^{[4
]}

Canzian, Federico ^{[33
]}

Campa, Daniele ^{[1
]}

机构：

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

[2] Palacky Univ Olomouc, Fac Med & Dent, Dept Oncol, Olomouc, Czech Republic

[3] Pisa Univ Hosp, Div Gen & Transplant Surg, Pisa, Italy

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

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

[6] Natl Inst Publ Hlth, Ctr Toxicol & Hlth Safety, Toxicogen Unit, Prague, Czech Republic

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

[8] Univ Vita Salute San Raffaele, IRCCS San Raffaele Sci Inst, Gastroenterol & Gastrointestinal Endoscopy Unit, Milan, Italy

[9] IRCCS Humanitas Res Hosp, Dept Gastroenterol, Endoscop Unit, Milan, Italy

[10] Potenza Med Cty Assoc, Potenza, Italy

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

[12] Univ Pecs, Janos Szentagothai Res Ctr, Pecs, Hungary

[13] Univ Szeged, Ctr Translat Med, Dept Med, Szeged, Hungary

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

[15] Ist Ricovero & Cura Carattere Sci IRCCS, San Raffaele Sci Inst, Pancreatobiliary Endoscopy & Endosonog Div, Pancreas Translat & Clin Res Ctr, Milan, Italy

[16] St Andrea Hosp, Digest & Liver Dis Unit, Rome, Italy

[17] Fdn IRCCS Casa Sollievo Sofferenza Hosp, Div Gastroenterol & Res Lab, Foggia, Italy

[18] Univ Padua, Dept Surg Oncol & Gastroenterol, Padua, Italy

[19] Erasmus MC Univ, Dept Surg, Med Ctr, Rotterdam, Netherlands

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

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

[22] Czech Acad Sci, Dept Mol Biol Canc, Inst Expt Med, Prague, Czech Republic

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

[24] Charles Univ Prague, Fac Med 1, Inst Biol & Med Genet, Prague, Czech Republic

[25] Univ Hosp Olomouc, Dept Surg 1, Olomouc, Czech Republic

[26] Semmelweis Univ, Ctr Translat Med, Budapest, Hungary

[27] Semmelweis Univ, Heart & Vasc Ctr, Div Pancreat Dis, Budapest, Hungary

[28] Univ Amsterdam, Canc Ctr Amsterdam, Dept Surg, Amsterdam UMC, Amsterdam, Netherlands

[29] Azienda USL Toscana Nord Ovest, Oncol Dept Massa Carrara, Carrara, Italy

[30] Univ Padua, Dept Med, Padua, Italy

[31] Carol Davila Univ Med & Pharm, Bucharest, Romania

[32] Semmelweis Univ, Dept Internal Med & Oncol, Budapest, Hungary

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

来源：

INTERNATIONAL JOURNAL OF CANCER | 2023年 / 153卷 / 02期

关键词：

association study; genetic susceptibility; pancreatic ductal adenocarcinoma; single nucleotide polymorphisms; SUSCEPTIBILITY;

D O I：

10.1002/ijc.34383

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Genes carrying high-penetrance germline mutations may also be associated with cancer susceptibility through common low-penetrance genetic variants. To increase the knowledge on genetic pancreatic ductal adenocarcinoma (PDAC) aetiology, the common genetic variability of PDAC familial genes was analysed in our study. We conducted a multiphase study analysing 7745 single nucleotide polymorphisms (SNPs) from 29 genes reported to harbour a high-penetrance PDAC-associated mutation in at least one published study. To assess the effect of the SNPs on PDAC risk, a total of 14 666 PDAC cases and 221 897 controls across five different studies were analysed. The T allele of the rs1412832 polymorphism, that is situated in the CDKN2B-AS1/ANRIL, showed a genome-wide significant association with increased risk of developing PDAC (OR = 1.11, 95% CI = 1.07-1.15, P = 5.25 x 10(-9)). CDKN2B-AS1/ANRIL is a long noncoding RNA, situated in 9p21.3, and regulates many target genes, among which CDKN2A (p16) that frequently shows deleterious somatic and germline mutations and deregulation in PDAC. Our results strongly support the role of the genetic variability of the 9p21.3 region in PDAC aetiopathogenesis and highlight the importance of secondary analysis as a tool for discovering new risk loci in complex human diseases.

引用

页码：373 / 379

页数：7

共 27 条

[1] Crosstalk of Cyclin-dependent kinase inhibitor 1A (CDKN1A) gene polymorphism with p53 and CCND1 polymorphism in breast cancer
Akhter, N.
Dar, S. A.
Haque, S.
Wahid, M.
Jawed, A.
Akhtar, S.
Alharbi, R. A.
Sindi, A. A. A.
Alruwetei, A.
Choudhry, H. M. Zubair
Ahmad, A.
[J]. EUROPEAN REVIEW FOR MEDICAL AND PHARMACOLOGICAL SCIENCES, 2021, 25 (12) : 4258 - 4273
[2] Health influenced by genetics: A first comprehensive analysis of breast cancer high and moderate penetrance susceptibility genes in the Tunisian population
Boujemaa, Maroua
Mighri, Najah
Chouchane, Lotfi
Boubaker, Mohamed Samir
Abdelhak, Sonia
Boussen, Hamouda
Hamdi, Yosr
[J]. PLOS ONE, 2022, 17 (03):
[3] Annotation of functional variation in personal genomes using RegulomeDB
Boyle, Alan P.
Hong, Eurie L.
Hariharan, Manoj
Cheng, Yong
Schaub, Marc A.
Kasowski, Maya
Karczewski, Konrad J.
Park, Julie
Hitz, Benjamin C.
Weng, Shuai
Cherry, J. Michael
Snyder, Michael
[J]. GENOME RESEARCH, 2012, 22 (09) : 1790 - 1797
[4] The cell cycle regulatory gene polymorphisms TP53 (rs1042522) and MDM2 (rs2279744) in lung cancer: a meta-analysis
Bulgakova, O.
Kussainova, A.
Bersimbaev, R.
[J]. VAVILOVSKII ZHURNAL GENETIKI I SELEKTSII, 2020, 24 (07): : 777 - 784
[5] 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
[6] 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
[7] Lack of Replication of Seven Pancreatic Cancer Susceptibility Loci Identified in Two Asian Populations
Campa, Daniele
Rizzato, Cosmeri
Bauer, Andrea S.
Werner, Jens
Capurso, Gabriele
Costello, Eithne
Talar-Wojnarowska, Renata
Jamroziak, Krzysztof
Pezzilli, Raffaele
Gazouli, Maria
Khaw, Kay-Tee
Key, Timothy J.
Bambi, Franco
Mohelnikova-Duchonova, Beatrice
Heller, Anette
Landi, Stefano
Vodickova, Ludmila
Theodoropoulos, George
Bugert, Peter
Vodicka, Pavel
Hoheisel, Joerg D.
Delle Fave, Gianfranco
Neoptolemos, John P.
Soucek, Pavel
Buechler, Markus W.
Giese, Nathalia
Canzian, Federico
[J]. CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION, 2013, 22 (02) : 320 - 323
[8] Genetic susceptibility to pancreatic cancer and its functional characterisation: The PANcreatic Disease ReseArch (PANDoRA) consortium
Campa, Daniele
Rizzato, Cosmeri
Capurso, Gabriele
Giese, Nathalia
Funel, Niccola
Greenhalf, William
Soucek, Pavel
Gazouli, Maria
Pezzilli, Raffaele
Pasquali, Claudio
Talar-Wojnarowska, Renata
Cantore, Maurizio
Andriulli, Angelo
Scarpa, Aldo
Jamroziak, Krzysztof
Delle Fave, Gianfranco
Costello, Eithne
Khaw, Kay-Tee
Heller, Anette
Key, Tim J.
Theodoropoulos, George
Malecka-Panas, Ewa
Mambrini, Andrea
Bambi, Franco
Landi, Stefano
Pedrazzoli, Sergio
Bassi, Claudio
Pacetti, Paola
Piepoli, Ada
Tavano, Francesca
di Sebastiano, Pierluigi
Vodickova, Ludmila
Basso, Daniela
Plebani, Mario
Fogar, Paola
Buechler, Markus W.
Bugert, Peter
Vodicka, Pavel
Boggi, Ugo
Neoptolemos, John P.
Werner, Jens
Canzian, Federico
[J]. DIGESTIVE AND LIVER DISEASE, 2013, 45 (02) : 95 - 99
[9] Genome-wide scan of long noncoding RNA single nucleotide polymorphisms and pancreatic cancer susceptibility
Corradi, Chiara
Gentiluomo, Manuel
Gajdan, Laszlo
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, Niccolo
Malecka-Panas, Ewa
Hegyi, Peter
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
[J]. INTERNATIONAL JOURNAL OF CANCER, 2021, 148 (11) : 2779 - 2788
[10] Cancer statistics for the year 2020: An overview
Ferlay, Jacques
Colombet, Murielle
Soerjomataram, Isabelle
Parkin, Donald M.
Pineros, Marion
Znaor, Ariana
Bray, Freddie
[J]. INTERNATIONAL JOURNAL OF CANCER, 2021, 149 (04) : 778 - 789

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