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

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