Do pancreatic cancer and chronic pancreatitis share the same genetic risk factors?

TY - JOUR

T1 - Do pancreatic cancer and chronic pancreatitis share the same genetic risk factors?

T2 - A PANcreatic Disease ReseArch (PANDoRA) consortium investigation

AU - Campa, Daniele

AU - Pastore, Manuela

AU - Capurso, Gabriele

AU - Hackert, Thilo

AU - Di Leo, Milena

AU - Izbicki, Jakob R

AU - Khaw, Kay-Tee

AU - Gioffreda, Domenica

AU - Kupcinskas, Juozas

AU - Pasquali, Claudio

AU - Macinga, Peter

AU - Kaaks, Rudolf

AU - Stigliano, Serena

AU - Peeters, Petra H

AU - Key, Timothy J

AU - Talar-Wojnarowska, Renata

AU - Vodicka, Pavel

AU - Valente, Roberto

AU - Vashist, Yogesh K

AU - Salvia, Roberto

AU - Papaconstantinou, Ioannis

AU - Shimizu, Yasuhiro

AU - Valsuani, Chiara

AU - Zambon, Carlo Federico

AU - Gazouli, Maria

AU - Valantiene, Irena

AU - Niesen, Willem

AU - Mohelnikova-Duchonova, Beatrice

AU - Hara, Kazuo

AU - Soucek, Pavel

AU - Malecka-Panas, Ewa

AU - Bueno-de-Mesquita, H B As

AU - Johnson, Theron

AU - Brenner, Herman

AU - Tavano, Francesca

AU - Fogar, Paola

AU - Ito, Hidemi

AU - Sperti, Cosimo

AU - Butterbach, Katja

AU - Latiano, Anna

AU - Andriulli, Angelo

AU - Cavestro, Giulia Martina

AU - Busch, Olivier R C

AU - Dijk, Frederike

AU - Greenhalf, William

AU - Matsuo, Keitaro

AU - Lombardo, Carlo

AU - Strobel, Oliver

AU - König, Anna-Katharina

AU - Cuk, Katarina

AU - Strothmann, Hendrik

AU - Katzke, Verena

AU - Cantore, Maurizio

AU - Mambrini, Andrea

AU - Oliverius, Martin

AU - Pezzilli, Raffaele

AU - Landi, Stefano

AU - Canzian, Federico

N1 - © 2017 UICC.

PY - 2018/1/15

Y1 - 2018/1/15

N2 - 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.

AB - 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.

KW - Adenocarcinoma/genetics

KW - Adult

KW - Aged

KW - Biomarkers, Tumor/genetics

KW - Carcinoma, Pancreatic Ductal/genetics

KW - Case-Control Studies

KW - Female

KW - Follow-Up Studies

KW - Humans

KW - Male

KW - Middle Aged

KW - Nuclear Proteins/genetics

KW - Pancreatic Neoplasms/genetics

KW - Pancreatitis, Chronic/genetics

KW - Polymorphism, Single Nucleotide

KW - Prognosis

KW - Retrospective Studies

KW - Risk Factors

KW - Trypsin/genetics

KW - Trypsinogen/genetics

U2 - 10.1002/ijc.31047

DO - 10.1002/ijc.31047

M3 - SCORING: Journal article

C2 - 28913878

VL - 142

SP - 290

EP - 296

JO - INT J CANCER

JF - INT J CANCER

SN - 0020-7136

IS - 2

ER -