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

International Journal of Cancer, October 2017

28913878

Daniele Campa, Manuela Pastore, Gabriele Capurso, Thilo Hackert, Milena Di Leo, Jakob R Izbicki, Kay-Tee Khaw, Domenica Gioffreda, Juozas Kupcinskas, Claudio Pasquali, Peter Macinga, Rudolf Kaaks, Serena Stigliano, Petra H Peeters, Timothy J Key, Renata Talar-Wojnarowska, Pavel Vodicka, Roberto Valente, Yogesh K Vashist, Roberto Salvia, Ioannis Papaconstantinou, Yasuhiro Shimizu, Chiara Valsuani, Carlo Federico Zambon, Maria Gazouli, Irena Valantiene, Willem Niesen, Beatrice Mohelnikova-Duchonova, Kazuo Hara, Pavel Soucek, Ewa Malecka-Panas, H B As Bueno-de-Mesquita, Theron Johnson, Herman Brenner, Francesca Tavano, Paola Fogar, Hidemi Ito, Cosimo Sperti, Katja Butterbach, Anna Latiano, Angelo Andriulli, Giulia Martina Cavestro, Olivier R C Busch, Frederike Dijk, William Greenhalf, Keitaro Matsuo, Carlo Lombardo, Oliver Strobel, Anna-Katharina König, Katarina Cuk, Hendrik Strothmann, Verena Katzke, Maurizio Cantore, Andrea Mambrini, Martin Oliverius, Raffaele Pezzilli, Stefano Landi, Federico Canzian

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.