Polygenic and multifactorial scores for pancreatic ductal adenocarcinoma risk prediction
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Polygenic and multifactorial scores for pancreatic ductal adenocarcinoma risk prediction. / Galeotti, Alice Alessandra; Gentiluomo, Manuel; 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, Orazio; 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, Maria; Vodickova, Ludmila; Soucek, Pavel; Gioffreda, Domenica; Gemignani, Federica; Brenner, Hermann; Strobel, Oliver; Büchler, Markus; Vodicka, Pavel; Paiella, Salvatore; Canzian, Federico; Campa, Daniele.
In: J MED GENET, Vol. 58, No. 6, 06.2021, p. 369-377.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Polygenic and multifactorial scores for pancreatic ductal adenocarcinoma risk prediction
AU - Galeotti, Alice Alessandra
AU - Gentiluomo, Manuel
AU - Rizzato, Cosmeri
AU - Obazee, Ofure
AU - Neoptolemos, John P
AU - Pasquali, Claudio
AU - Nentwich, Michael
AU - Cavestro, Giulia Martina
AU - Pezzilli, Raffaele
AU - Greenhalf, William
AU - Holleczek, Bernd
AU - Schroeder, Cornelia
AU - Schöttker, Ben
AU - Ivanauskas, Audrius
AU - Ginocchi, Laura
AU - Key, Timothy J
AU - Hegyi, Péter
AU - Archibugi, Livia
AU - Darvasi, Erika
AU - Basso, Daniela
AU - Sperti, Cosimo
AU - Bijlsma, Maarten F
AU - Palmieri, Orazio
AU - Hlavac, Viktor
AU - Talar-Wojnarowska, Renata
AU - Mohelnikova-Duchonova, Beatrice
AU - Hackert, Thilo
AU - Vashist, Yogesh
AU - Strouhal, Ondrej
AU - van Laarhoven, Hanneke
AU - Tavano, Francesca
AU - Lovecek, Martin
AU - Dervenis, Christos
AU - Izbéki, Ferenc
AU - Padoan, Andrea
AU - Małecka-Panas, Ewa
AU - Maiello, Evaristo
AU - Vanella, Giuseppe
AU - Capurso, Gabriele
AU - Izbicki, Jakob R
AU - Theodoropoulos, George E
AU - Jamroziak, Krzysztof
AU - Katzke, Verena
AU - Kaaks, Rudolf
AU - Mambrini, Andrea
AU - Papanikolaou, Ioannis S
AU - Szmola, Richárd
AU - Szentesi, Andrea
AU - Kupcinskas, Juozas
AU - Bursi, Simona
AU - Costello, Eithne
AU - Boggi, Ugo
AU - Milanetto, Anna Caterina
AU - Landi, Stefano
AU - Gazouli, Maria
AU - Vodickova, Ludmila
AU - Soucek, Pavel
AU - Gioffreda, Domenica
AU - Gemignani, Federica
AU - Brenner, Hermann
AU - Strobel, Oliver
AU - Büchler, Markus
AU - Vodicka, Pavel
AU - Paiella, Salvatore
AU - Canzian, Federico
AU - Campa, Daniele
N1 - © Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.
PY - 2021/6
Y1 - 2021/6
N2 - 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.
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.
U2 - 10.1136/jmedgenet-2020-106961
DO - 10.1136/jmedgenet-2020-106961
M3 - SCORING: Journal article
C2 - 32591343
VL - 58
SP - 369
EP - 377
JO - J MED GENET
JF - J MED GENET
SN - 0022-2593
IS - 6
ER -