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Polygenic and multifactorial scores for pancreatic ductal adenocarcinoma risk prediction

Authors :
John P. Neoptolemos
Markus W. Büchler
Jakob R. Izbicki
Ben Schöttker
Cosmeri Rizzato
Cornelia Schroeder
Salvatore Paiella
Hanneke W. M. van Laarhoven
William Greenhalf
Simona Bursi
Renata Talar-Wojnarowska
Christos Dervenis
Ludmila Vodickova
Francesca Tavano
Giulia Martina Cavestro
Thilo Hackert
Claudio Pasquali
Ewa Małecka-Panas
Gabriele Capurso
Andrea Mambrini
Daniele Campa
Andrea Padoan
Ioannis S. Papanikolaou
Raffaele Pezzilli
Péter Hegyi
Beatrice Mohelnikova-Duchonova
Federica Gemignani
Michael F. Nentwich
Pavel Vodicka
Stefano Landi
Richárd Szmola
Anna Caterina Milanetto
Eithne Costello
Rudolf Kaaks
Laura Ginocchi
Bernd Holleczek
Erika Darvasi
Verena Katzke
Evaristo Maiello
Manuel Gentiluomo
Ondrej Strouhal
Orazio Palmieri
Juozas Kupcinskas
Alice Alessandra Galeotti
Viktor Hlavac
George Theodoropoulos
Audrius Ivanauskas
Maria Gazouli
Ferenc Izbéki
Federico Canzian
Oliver Strobel
Ofure Obazee
Martin Lovecek
Timothy J. Key
Domenica Gioffreda
Pavel Soucek
Ugo Boggi
Krzysztof Jamroziak
Cosimo Sperti
Maarten F. Bijlsma
Yogesh K. Vashist
Andrea Szentesi
Hermann Brenner
Livia Archibugi
Giuseppe Vanella
Daniela Basso
Radiotherapy
Center of Experimental and Molecular Medicine
CCA - Cancer Treatment and Quality of Life
Oncology
AGEM - Amsterdam Gastroenterology Endocrinology Metabolism
Galeotti, A. A.
Gentiluomo, M.
Rizzato, C.
Obazee, O.
Neoptolemos, J. P.
Pasquali, C.
Nentwich, M.
Cavestro, G. M.
Pezzilli, R.
Greenhalf, W.
Holleczek, B.
Schroeder, C.
Schottker, B.
Ivanauskas, A.
Ginocchi, L.
Key, T. J.
Hegyi, P.
Archibugi, L.
Darvasi, E.
Basso, D.
Sperti, C.
Bijlsma, M. F.
Palmieri, O.
Hlavac, V.
Talar-Wojnarowska, R.
Mohelnikova-Duchonova, B.
Hackert, T.
Vashist, Y.
Strouhal, O.
Van Laarhoven, H.
Tavano, F.
Lovecek, M.
Dervenis, C.
Izbeki, F.
Padoan, A.
Malecka-Panas, E.
Maiello, E.
Vanella, G.
Capurso, G.
Izbicki, J. R.
Theodoropoulos, G. E.
Jamroziak, K.
Katzke, V.
Kaaks, R.
Mambrini, A.
Papanikolaou, I. S.
Szmola, R.
Szentesi, A.
Kupcinskas, J.
Bursi, S.
Costello, E.
Boggi, U.
Milanetto, A. C.
Landi, S.
Gazouli, M.
Vodickova, L.
Soucek, P.
Gioffreda, D.
Gemignani, F.
Brenner, H.
Strobel, O.
Buchler, M.
Vodicka, P.
Paiella, S.
Canzian, F.
Campa, D.
Source :
Journal of medical genetics, 58(6), 369-377. BMJ Publishing Group, JOURNAL OF MEDICAL GENETICS
Publication Year :
2020

Abstract

BackgroundMost cases of pancreatic ductal adenocarcinoma (PDAC) are asymptomatic in early stages, and the disease is typically diagnosed in advanced phases, resulting in very high mortality. Tools to identify individuals at high risk of developing PDAC would be useful to improve chances of early detection.ObjectiveWe generated a polygenic risk score (PRS) for PDAC risk prediction, combining the effect of known risk SNPs, and carried out an exploratory analysis of a multifactorial score.MethodsWe tested the associations of the individual known risk SNPs on up to 2851 PDAC cases and 4810 controls of European origin from the PANcreatic Disease ReseArch (PANDoRA) consortium. Thirty risk SNPs were included in a PRS, which was computed on the subset of subjects that had 100% call rate, consisting of 839 cases and 2040 controls in PANDoRA and 6420 cases and 4889 controls from the previously published Pancreatic Cancer Cohort Consortium I–III and Pancreatic Cancer Case-Control Consortium genome-wide association studies. Additional exploratory multifactorial scores were constructed by complementing the genetic score with smoking and diabetes.ResultsThe scores were associated with increased PDAC risk and reached high statistical significance (OR=2.70, 95% CI 1.99 to 3.68, p=2.54×10−10 highest vs lowest quintile of the weighted PRS, and OR=14.37, 95% CI 5.57 to 37.09, p=3.64×10−8, highest vs lowest quintile of the weighted multifactorial score).ConclusionWe found a highly significant association between a PRS and PDAC risk, which explains more than individual SNPs and is a step forward in the direction of the construction of a tool for risk stratification in the population.

Details

Language :
English
ISSN :
00222593
Database :
OpenAIRE
Journal :
Journal of medical genetics, 58(6), 369-377. BMJ Publishing Group, JOURNAL OF MEDICAL GENETICS
Accession number :
edsair.doi.dedup.....a267bd63e2a9e7418632e88a73d56f47