Do pancreatic cancer and chronic pancreatitis share the same genetic risk factors? A PANcreatic Disease ReseArch (PANDoRA) consortium investigation.

2.50
Hdl Handle:
http://hdl.handle.net/10029/621113
Title:
Do pancreatic cancer and chronic pancreatitis share the same genetic risk factors? A PANcreatic Disease ReseArch (PANDoRA) consortium investigation.
Authors:
Campa, Daniele; Pastore, Manuela; Capurso, Gabriele; Hackert, Thilo; Di Leo, Milena; Izbicki, Jakob R; Khaw, Kay-Tee; Gioffreda, Domenica; Kupcinskas, Juozas; Pasquali, Claudio; Macinga, Peter; Kaaks, Rudolf; Stigliano, Serena; Peeters, Petra H; Key, Timothy J; Talar-Wojnarowska, Renata; Vodicka, Pavel; Valente, Roberto; Vashist, Yogesh K; Salvia, Roberto; Papaconstantinou, Ioannis; Shimizu, Yasuhiro; Valsuani, Chiara; Zambon, Carlo Federico; Gazouli, Maria; Valantiene, Irena; Niesen, Willem; Mohelnikova-Duchonova, Beatrice; Hara, Kazuo; Soucek, Pavel; Malecka-Panas, Ewa; Bueno-de-Mesquita, H B As; Johnson, Theron; Brenner, Herman; Tavano, Francesca; Fogar, Paola; Ito, Hidemi; Sperti, Cosimo; Butterbach, Katja; Latiano, Anna; Andriulli, Angelo; Cavestro, Giulia Martina; Busch, Olivier R C; Dijk, Frederike; Greenhalf, William; Matsuo, Keitaro; Lombardo, Carlo; Strobel, Oliver; König, Anna-Katharina; Cuk, Katarina; Strothmann, Hendrik; Katzke, Verena; Cantore, Maurizio; Mambrini, Andrea; Oliverius, Martin; Pezzilli, Raffaele; Landi, Stefano; Canzian, Federico
Abstract:
Pancreatic ductal adenocarcinoma (PDAC) is a very aggressive tumor with a five-year survival of less than 6%. Chronic pancreatitis (CP), an inflammatory process in of the pancreas, is a strong risk factor for PDAC. Several genetic polymorphisms have been discovered as susceptibility loci for both CP and PDAC. Since CP and PDAC share a consistent number of epidemiologic risk factors, the aim of this study was to investigate whether specific CP risk loci also contribute to PDAC susceptibility. We selected five common SNPs (rs11988997, rs379742, rs10273639, rs2995271 and rs12688220) that were identified as susceptibility markers for CP and analyzed them in 2,914 PDAC cases, 356 CP cases and 5,596 controls retrospectively collected in the context of the international PANDoRA consortium. We found a weak association between the minor allele of the PRSS1-PRSS2-rs10273639 and an increased risk of developing PDAC (ORhomozygous  = 1.19, 95% CI 1.02-1.38, p = 0.023). Additionally all the SNPs confirmed statistically significant associations with risk of developing CP, the strongest being PRSS1-PRSS2-rs10273639 (ORheterozygous  = 0.51, 95% CI 0.39-0.67, p = 1.10 × 10-6 ) and MORC4-rs 12837024 (ORhomozygous  = 2.07 (1.55-2.77, ptrend  = 0.7 × 10-11 ). Taken together, the results from our study do not support variants rs11988997, rs379742, rs10273639, rs2995271 and rs12688220 as strong predictors of PDAC risk, but further support the role of these SNPs in CP susceptibility. Our study suggests that CP and PDAC probably do not share genetic susceptibility, at least in terms of high frequency variants.
Citation:
Do pancreatic cancer and chronic pancreatitis share the same genetic risk factors? A PANcreatic Disease ReseArch (PANDoRA) consortium investigation. 2018, 142 (2):290-296 Int. J. Cancer
Journal:
Int J Cancer 2018, 142(2):290-6
Issue Date:
15-Jan-2018
URI:
http://hdl.handle.net/10029/621113
DOI:
10.1002/ijc.31047
PubMed ID:
28913878
Type:
Article
Language:
en
ISSN:
1097-0215
Appears in Collections:
Miscellaneous

Full metadata record

DC FieldValue Language
dc.contributor.authorCampa, Danieleen
dc.contributor.authorPastore, Manuelaen
dc.contributor.authorCapurso, Gabrieleen
dc.contributor.authorHackert, Thiloen
dc.contributor.authorDi Leo, Milenaen
dc.contributor.authorIzbicki, Jakob Ren
dc.contributor.authorKhaw, Kay-Teeen
dc.contributor.authorGioffreda, Domenicaen
dc.contributor.authorKupcinskas, Juozasen
dc.contributor.authorPasquali, Claudioen
dc.contributor.authorMacinga, Peteren
dc.contributor.authorKaaks, Rudolfen
dc.contributor.authorStigliano, Serenaen
dc.contributor.authorPeeters, Petra Hen
dc.contributor.authorKey, Timothy Jen
dc.contributor.authorTalar-Wojnarowska, Renataen
dc.contributor.authorVodicka, Pavelen
dc.contributor.authorValente, Robertoen
dc.contributor.authorVashist, Yogesh Ken
dc.contributor.authorSalvia, Robertoen
dc.contributor.authorPapaconstantinou, Ioannisen
dc.contributor.authorShimizu, Yasuhiroen
dc.contributor.authorValsuani, Chiaraen
dc.contributor.authorZambon, Carlo Federicoen
dc.contributor.authorGazouli, Mariaen
dc.contributor.authorValantiene, Irenaen
dc.contributor.authorNiesen, Willemen
dc.contributor.authorMohelnikova-Duchonova, Beatriceen
dc.contributor.authorHara, Kazuoen
dc.contributor.authorSoucek, Pavelen
dc.contributor.authorMalecka-Panas, Ewaen
dc.contributor.authorBueno-de-Mesquita, H B Asen
dc.contributor.authorJohnson, Theronen
dc.contributor.authorBrenner, Hermanen
dc.contributor.authorTavano, Francescaen
dc.contributor.authorFogar, Paolaen
dc.contributor.authorIto, Hidemien
dc.contributor.authorSperti, Cosimoen
dc.contributor.authorButterbach, Katjaen
dc.contributor.authorLatiano, Annaen
dc.contributor.authorAndriulli, Angeloen
dc.contributor.authorCavestro, Giulia Martinaen
dc.contributor.authorBusch, Olivier R Cen
dc.contributor.authorDijk, Frederikeen
dc.contributor.authorGreenhalf, Williamen
dc.contributor.authorMatsuo, Keitaroen
dc.contributor.authorLombardo, Carloen
dc.contributor.authorStrobel, Oliveren
dc.contributor.authorKönig, Anna-Katharinaen
dc.contributor.authorCuk, Katarinaen
dc.contributor.authorStrothmann, Hendriken
dc.contributor.authorKatzke, Verenaen
dc.contributor.authorCantore, Maurizioen
dc.contributor.authorMambrini, Andreaen
dc.contributor.authorOliverius, Martinen
dc.contributor.authorPezzilli, Raffaeleen
dc.contributor.authorLandi, Stefanoen
dc.contributor.authorCanzian, Federicoen
dc.date.accessioned2018-01-10T07:37:59Z-
dc.date.available2018-01-10T07:37:59Z-
dc.date.issued2018-01-15-
dc.identifier.citationDo pancreatic cancer and chronic pancreatitis share the same genetic risk factors? A PANcreatic Disease ReseArch (PANDoRA) consortium investigation. 2018, 142 (2):290-296 Int. J. Canceren
dc.identifier.issn1097-0215-
dc.identifier.pmid28913878-
dc.identifier.doi10.1002/ijc.31047-
dc.identifier.urihttp://hdl.handle.net/10029/621113-
dc.description.abstractPancreatic ductal adenocarcinoma (PDAC) is a very aggressive tumor with a five-year survival of less than 6%. Chronic pancreatitis (CP), an inflammatory process in of the pancreas, is a strong risk factor for PDAC. Several genetic polymorphisms have been discovered as susceptibility loci for both CP and PDAC. Since CP and PDAC share a consistent number of epidemiologic risk factors, the aim of this study was to investigate whether specific CP risk loci also contribute to PDAC susceptibility. We selected five common SNPs (rs11988997, rs379742, rs10273639, rs2995271 and rs12688220) that were identified as susceptibility markers for CP and analyzed them in 2,914 PDAC cases, 356 CP cases and 5,596 controls retrospectively collected in the context of the international PANDoRA consortium. We found a weak association between the minor allele of the PRSS1-PRSS2-rs10273639 and an increased risk of developing PDAC (ORhomozygous  = 1.19, 95% CI 1.02-1.38, p = 0.023). Additionally all the SNPs confirmed statistically significant associations with risk of developing CP, the strongest being PRSS1-PRSS2-rs10273639 (ORheterozygous  = 0.51, 95% CI 0.39-0.67, p = 1.10 × 10-6 ) and MORC4-rs 12837024 (ORhomozygous  = 2.07 (1.55-2.77, ptrend  = 0.7 × 10-11 ). Taken together, the results from our study do not support variants rs11988997, rs379742, rs10273639, rs2995271 and rs12688220 as strong predictors of PDAC risk, but further support the role of these SNPs in CP susceptibility. Our study suggests that CP and PDAC probably do not share genetic susceptibility, at least in terms of high frequency variants.en
dc.language.isoenen
dc.rightsArchived with thanks to International journal of canceren
dc.subject.meshAdenocarcinoma-
dc.subject.meshAdult-
dc.subject.meshAged-
dc.subject.meshBiomarkers, Tumor-
dc.subject.meshCarcinoma, Pancreatic Ductal-
dc.subject.meshCase-Control Studies-
dc.subject.meshFemale-
dc.subject.meshFollow-Up Studies-
dc.subject.meshHumans-
dc.subject.meshMale-
dc.subject.meshMiddle Aged-
dc.subject.meshNuclear Proteins-
dc.subject.meshPancreatic Neoplasms-
dc.subject.meshPancreatitis, Chronic-
dc.subject.meshPolymorphism, Single Nucleotide-
dc.subject.meshPrognosis-
dc.subject.meshRetrospective Studies-
dc.subject.meshRisk Factors-
dc.subject.meshTrypsin-
dc.subject.meshTrypsinogen-
dc.titleDo pancreatic cancer and chronic pancreatitis share the same genetic risk factors? A PANcreatic Disease ReseArch (PANDoRA) consortium investigation.en
dc.typeArticleen
dc.identifier.journalInt J Cancer 2018, 142(2):290-6en

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