RT Journal Article
SR Electronic
T1 Polygenic and multifactorial scores for pancreatic ductal adenocarcinoma risk prediction
JF Journal of Medical Genetics
JO J Med Genet
FD BMJ Publishing Group Ltd
SP 369
OP 377
DO 10.1136/jmedgenet-2020-106961
VO 58
IS 6
A1 Alice Alessandra Galeotti
A1 Manuel Gentiluomo
A1 Cosmeri Rizzato
A1 Ofure Obazee
A1 John P Neoptolemos
A1 Claudio Pasquali
A1 Michael Nentwich
A1 Giulia Martina Cavestro
A1 Raffaele Pezzilli
A1 William Greenhalf
A1 Bernd Holleczek
A1 Cornelia Schroeder
A1 Ben Schöttker
A1 Audrius Ivanauskas
A1 Laura Ginocchi
A1 Timothy J Key
A1 Péter Hegyi
A1 Livia Archibugi
A1 Erika Darvasi
A1 Daniela Basso
A1 Cosimo Sperti
A1 Maarten F Bijlsma
A1 Orazio Palmieri
A1 Viktor Hlavac
A1 Renata Talar-Wojnarowska
A1 Beatrice Mohelnikova-Duchonova
A1 Thilo Hackert
A1 Yogesh Vashist
A1 Ondrej Strouhal
A1 Hanneke van Laarhoven
A1 Francesca Tavano
A1 Martin Lovecek
A1 Christos Dervenis
A1 Ferenc Izbéki
A1 Andrea Padoan
A1 Ewa Małecka-Panas
A1 Evaristo Maiello
A1 Giuseppe Vanella
A1 Gabriele Capurso
A1 Jakob R Izbicki
A1 George E Theodoropoulos
A1 Krzysztof Jamroziak
A1 Verena Katzke
A1 Rudolf Kaaks
A1 Andrea Mambrini
A1 Ioannis S Papanikolaou
A1 Richárd Szmola
A1 Andrea Szentesi
A1 Juozas Kupcinskas
A1 Simona Bursi
A1 Eithne Costello
A1 Ugo Boggi
A1 Anna Caterina Milanetto
A1 Stefano Landi
A1 Maria Gazouli
A1 Ludmila Vodickova
A1 Pavel Soucek
A1 Domenica Gioffreda
A1 Federica Gemignani
A1 Hermann Brenner
A1 Oliver Strobel
A1 Markus Büchler
A1 Pavel Vodicka
A1 Salvatore Paiella
A1 Federico Canzian
A1 Daniele Campa
YR 2021
UL http://jmg.bmj.com/content/58/6/369.abstract
AB Background Most 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.Objective We 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.Methods We 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.Results The 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).Conclusion We 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.Data are available upon reasonable request. Data may be obtained from a third party and are not publicly available. The data supporting the findings of this study are available upon reasonable request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions. Sharing data will be conditional to approval by the PANDoRA steering committee and, if needed, to additional approval of the competent Institutional Review Boards.