5 years ago

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

Serena Stigliano, Maurizio Cantore, Giulia Martina Cavestro, Roberto Valente, Hendrik Strothmann, H. Bas Bueno-De-Mesquita, Francesca Tavano, Milena Di Leo, Raffaele Pezzilli, Irena Valantiene, Andrea Mambrini, Petra H. Peeters, Rudolf Kaaks, Gabriele Capurso, Yogesh K. Vashist, Renata Talar-Wojnarowska, Hidemi Ito, Beatrice Mohelnikova-Duchonova, Claudio Pasquali, Oliver Strobel, Pavel Vodicka, Peter Macinga, Juozas Kupcinskas, Katarina Cuk, Herman Brenner, Theron Johnson, Kazuo Hara, Angelo Andriulli, Katja Butterbach, Ewa Malecka-Panas, Ioannis Papaconstantinou, Federico Canzian, Frederike Dijk, Olivier R.C. Busch, Maria Gazouli, Carlo Lombardo, Paola Fogar, Timothy J. Key, Jakob R. Izbicki, Pavel Soucek, Martin Oliverius, Thilo Hackert, Stefano Landi, William Greenhalf, Willem Niesen, Yasuhiro Shimizu, Keitaro Matsuo, Roberto Salvia, Chiara Valsuani, Manuela Pastore, Daniele Campa, Anna-Katharina König, Carlo Federico Zambon, Verena Katzke, Anna Latiano, Domenica Gioffreda, Cosimo Sperti, Kay-Tee Khaw
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 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=1.10x10−6) and MORC4-rs 12837024 (ORhomozygous=2.07 (1.55-2.77, ptrend=0.7x10−11). 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. This article is protected by copyright. All rights reserved.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1002/ijc.31047

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