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

作者信息

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

机构信息

Department of Biology, University of Pisa, Pisa, Italy.

Genomic Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany.

出版信息

Int J Cancer. 2018 Jan 15;142(2):290-296. doi: 10.1002/ijc.31047. Epub 2017 Oct 16.

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 (OR  = 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 (OR  = 0.51, 95% CI 0.39-0.67, p = 1.10 × 10 ) and MORC4-rs 12837024 (OR  = 2.07 (1.55-2.77, p  = 0.7 × 10 ). 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.

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