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, DanielePastore, 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
Type
ArticleLanguage
en
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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):290-6Publiekssamenvatting
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.PMID
28913878ae974a485f413a2113503eed53cd6c53
10.1002/ijc.31047
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