Polygenic and multifactorial scores for pancreatic ductal adenocarcinoma risk prediction
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Published:2020-06-26
Issue:6
Volume:58
Page:369-377
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ISSN:0022-2593
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Container-title:Journal of Medical Genetics
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language:en
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Short-container-title:J Med Genet
Author:
Galeotti Alice Alessandra, Gentiluomo ManuelORCID, Rizzato Cosmeri, Obazee Ofure, Neoptolemos John P, Pasquali Claudio, Nentwich Michael, Cavestro Giulia Martina, Pezzilli Raffaele, Greenhalf William, Holleczek Bernd, Schroeder Cornelia, Schöttker Ben, Ivanauskas Audrius, Ginocchi Laura, Key Timothy J, Hegyi Péter, Archibugi Livia, Darvasi Erika, Basso Daniela, Sperti Cosimo, Bijlsma Maarten F, Palmieri OrazioORCID, Hlavac Viktor, Talar-Wojnarowska Renata, Mohelnikova-Duchonova Beatrice, Hackert Thilo, Vashist Yogesh, Strouhal Ondrej, van Laarhoven Hanneke, Tavano Francesca, Lovecek Martin, Dervenis Christos, Izbéki Ferenc, Padoan Andrea, Małecka-Panas Ewa, Maiello Evaristo, Vanella Giuseppe, Capurso Gabriele, Izbicki Jakob R, Theodoropoulos George E, Jamroziak Krzysztof, Katzke Verena, Kaaks Rudolf, Mambrini Andrea, Papanikolaou Ioannis S, Szmola Richárd, Szentesi Andrea, Kupcinskas Juozas, Bursi Simona, Costello Eithne, Boggi Ugo, Milanetto Anna Caterina, Landi Stefano, Gazouli MariaORCID, Vodickova Ludmila, Soucek Pavel, Gioffreda Domenica, Gemignani Federica, Brenner Hermann, Strobel Oliver, Büchler Markus, Vodicka Pavel, Paiella Salvatore, Canzian Federico, Campa Daniele
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.
Funder
Fondazione Arpa Fondazione Tizzi
Subject
Genetics (clinical),Genetics
Cited by
37 articles.
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