Περίληψη:
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=2.54x10(-10)
highest vs lowest quintile of the weighted PRS, and OR=14.37, 95% CI
5.57 to 37.09, p=3.64x10(-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.
Συγγραφείς:
Galeotti, Alice Alessandra
Gentiluomo, Manuel
Rizzato, Cosmeri
and Obazee, Ofure
Neoptolemos, John P.
Pasquali, Claudio and
Nentwich, Michael
Cavestro, Giulia Martina
Pezzilli, Raffaele
and Greenhalf, William
Holleczek, Bernd
Schroeder, Cornelia and
Schottker, Ben
Ivanauskas, Audrius
Ginocchi, Laura
Key,
Timothy J.
Hegyi, Peter
Archibugi, Livia
Darvasi, Erika and
Basso, Daniela
Sperti, Cosimo
Bijlsma, Maarten F.
Palmieri,
Orazio
Hlavac, Viktor
Talar-Wojnarowska, Renata and
Mohelnikova-Duchonova, Beatrice
Hackert, Thilo
Vashist, Yogesh
and Strouhal, Ondrej
van Laarhoven, Hanneke
Tavano, Francesca
and Lovecek, Martin
Dervenis, Christos
Izbeki, Ferenc and
Padoan, Andrea
Malecka-Panas, Ewa
Maiello, Evaristo
Vanella,
Giuseppe
Capurso, Gabriele
Izbicki, Jakob R.
Theodoropoulos,
George E.
Jamroziak, Krzysztof
Katzke, Verena
Kaaks, Rudolf
and Mambrini, Andrea
Papanikolaou, Ioannis S.
Szmola, Richard
and Szentesi, Andrea
Kupcinskas, Juozas
Bursi, Simona and
Costello, Eithne
Boggi, Ugo
Milanetto, Anna Caterina
Landi,
Stefano
Gazouli, Maria
Vodickova, Ludmila
Soucek, Pavel and
Gioffreda, Domenica
Gemignani, Federica
Brenner, Hermann and
Strobel, Oliver
Buechler, Markus
Vodicka, Pavel
Paiella,
Salvatore
Canzian, Federico
Campa, Daniele
