Polygenic and multifactorial scores for pancreatic ductal adenocarcinoma risk prediction
Alice Alessandra Galeotti, Manuel Gentiluomo, Cosmeri Rizzato, Ofure Obazee, John P. Neoptolemos, Claudio Pasquali, Michael F. Nentwich, Giulia Martina Cavestro, Raffaele Pezzilli, William Greenhalf, Bernd Holleczek, Cornelia Schroeder, Ben Schöttker, Audrius Ivanauskas, Laura Ginocchi, Timothy J. Key, Péter Hegyi, Lívia Archibugi, Erika Darvasi, Daniela Basso, Cosimo Sperti, Maarten F. Bijlsma, Orazio Palmieri, Viktor Hlaváč, Renata Talar‐Wojnarowska, Beatrice Mohelníková-Duchoňová, Thilo Hackert, Yogesh K. Vashist, Ondřej Strouhal, Hanneke W.M. van Laarhoven, Francesca Tavano, Martin Loveček, Christos Dervenis, Ferenc Izbéki, Andrea Padoan, Ewa Małecka‐Panas, Evaristo Maiello, Giuseppe Vanella, Gabriele Capurso, Jakob R. Izbicki, George Theodoropoulos, Krzysztof Jamroziak, Verena Katzke, Rudolf Kaaks, Andrea Mambrini, Ioannis S. Papanikolaou, Richárd Szmola, Andrea Szentesi, Juozas Kupčinskas, S. Bursi, Eithne Costello, Ugo Boggi, Anna Caterina Milanetto, Stefano Landi, Maria Gazouli, Ľudmila Vodičková, Pavel Souček, Domenica Gioffreda, Federica Gemignani, Hermann Brenner, Oliver Strobel, Markus W. Büchler, Pavel Vodička, Salvatore Paiella, Federico Canzian, Daniele Campa
Abstract
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: , 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.