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

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    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
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    Type
    Article
    Language
    en
    
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    Title
    Do pancreatic cancer and chronic pancreatitis share the same genetic risk factors? A PANcreatic Disease ReseArch (PANDoRA) consortium investigation.
    Published in
    Int J Cancer 2018, 142(2):290-6
    Publiekssamenvatting
    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.
    DOI
    10.1002/ijc.31047
    PMID
    28913878
    URI
    http://hdl.handle.net/10029/621113
    ae974a485f413a2113503eed53cd6c53
    10.1002/ijc.31047
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