PT  - JOURNAL ARTICLE
AU  - Alice Alessandra Galeotti
AU  - Manuel Gentiluomo
AU  - Cosmeri Rizzato
AU  - Ofure Obazee
AU  - John P Neoptolemos
AU  - Claudio Pasquali
AU  - Michael Nentwich
AU  - Giulia Martina Cavestro
AU  - Raffaele Pezzilli
AU  - William Greenhalf
AU  - Bernd Holleczek
AU  - Cornelia Schroeder
AU  - Ben Schöttker
AU  - Audrius Ivanauskas
AU  - Laura Ginocchi
AU  - Timothy J Key
AU  - Péter Hegyi
AU  - Livia Archibugi
AU  - Erika Darvasi
AU  - Daniela Basso
AU  - Cosimo Sperti
AU  - Maarten F Bijlsma
AU  - Orazio Palmieri
AU  - Viktor Hlavac
AU  - Renata Talar-Wojnarowska
AU  - Beatrice Mohelnikova-Duchonova
AU  - Thilo Hackert
AU  - Yogesh Vashist
AU  - Ondrej Strouhal
AU  - Hanneke van Laarhoven
AU  - Francesca Tavano
AU  - Martin Lovecek
AU  - Christos Dervenis
AU  - Ferenc Izbéki
AU  - Andrea Padoan
AU  - Ewa Małecka-Panas
AU  - Evaristo Maiello
AU  - Giuseppe Vanella
AU  - Gabriele Capurso
AU  - Jakob R Izbicki
AU  - George E Theodoropoulos
AU  - Krzysztof Jamroziak
AU  - Verena Katzke
AU  - Rudolf Kaaks
AU  - Andrea Mambrini
AU  - Ioannis S Papanikolaou
AU  - Richárd Szmola
AU  - Andrea Szentesi
AU  - Juozas Kupcinskas
AU  - Simona Bursi
AU  - Eithne Costello
AU  - Ugo Boggi
AU  - Anna Caterina Milanetto
AU  - Stefano Landi
AU  - Maria Gazouli
AU  - Ludmila Vodickova
AU  - Pavel Soucek
AU  - Domenica Gioffreda
AU  - Federica Gemignani
AU  - Hermann Brenner
AU  - Oliver Strobel
AU  - Markus Büchler
AU  - Pavel Vodicka
AU  - Salvatore Paiella
AU  - Federico Canzian
AU  - Daniele Campa
TI  - Polygenic and multifactorial scores for pancreatic ductal adenocarcinoma risk prediction
AID  - 10.1136/jmedgenet-2020-106961
DP  - 2020 Jun 26
TA  - Journal of Medical Genetics
PG  - jmedgenet-2020-106961
4099  - http://jmg.bmj.com/content/early/2020/06/26/jmedgenet-2020-106961.short
4100  - http://jmg.bmj.com/content/early/2020/06/26/jmedgenet-2020-106961.full
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.