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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, Jahrgang 58, Nr. 6, 06.2021, S. 369-377.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Galeotti, AA, Gentiluomo, M, Rizzato, C, Obazee, O, Neoptolemos, JP, Pasquali, C, Nentwich, M, Cavestro, GM, Pezzilli, R, Greenhalf, W, Holleczek, B, Schroeder, C, Schöttker, B, Ivanauskas, A, Ginocchi, L, Key, TJ, Hegyi, P, Archibugi, L, Darvasi, E, Basso, D, Sperti, C, Bijlsma, MF, Palmieri, O, Hlavac, V, Talar-Wojnarowska, R, Mohelnikova-Duchonova, B, Hackert, T, Vashist, Y, Strouhal, O, van Laarhoven, H, Tavano, F, Lovecek, M, Dervenis, C, Izbéki, F, Padoan, A, Małecka-Panas, E, Maiello, E, Vanella, G, Capurso, G, Izbicki, JR, Theodoropoulos, GE, Jamroziak, K, Katzke, V, Kaaks, R, Mambrini, A, Papanikolaou, IS, Szmola, R, Szentesi, A, Kupcinskas, J, Bursi, S, Costello, E, Boggi, U, Milanetto, AC, Landi, S, Gazouli, M, Vodickova, L, Soucek, P, Gioffreda, D, Gemignani, F, Brenner, H, Strobel, O, Büchler, M, Vodicka, P, Paiella, S, Canzian, F & Campa, D 2021, 'Polygenic and multifactorial scores for pancreatic ductal adenocarcinoma risk prediction', J MED GENET, Jg. 58, Nr. 6, S. 369-377. https://doi.org/10.1136/jmedgenet-2020-106961

APA

Galeotti, A. A., Gentiluomo, M., Rizzato, C., Obazee, O., Neoptolemos, J. P., Pasquali, C., Nentwich, M., Cavestro, G. M., Pezzilli, R., Greenhalf, W., Holleczek, B., Schroeder, C., Schöttker, B., Ivanauskas, A., Ginocchi, L., Key, T. J., Hegyi, P., Archibugi, L., Darvasi, E., ... Campa, D. (2021). Polygenic and multifactorial scores for pancreatic ductal adenocarcinoma risk prediction. J MED GENET, 58(6), 369-377. https://doi.org/10.1136/jmedgenet-2020-106961

Vancouver

Galeotti AA, Gentiluomo M, Rizzato C, Obazee O, Neoptolemos JP, Pasquali C et al. Polygenic and multifactorial scores for pancreatic ductal adenocarcinoma risk prediction. J MED GENET. 2021 Jun;58(6):369-377. https://doi.org/10.1136/jmedgenet-2020-106961

Bibtex

@article{91ebc748b0014d038c74bf7d64888831,
title = "Polygenic and multifactorial scores for pancreatic ductal adenocarcinoma risk prediction",
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: 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.",
author = "Galeotti, {Alice Alessandra} and Manuel Gentiluomo and Cosmeri Rizzato and Ofure Obazee and Neoptolemos, {John P} and Claudio Pasquali and Michael Nentwich and Cavestro, {Giulia Martina} and Raffaele Pezzilli and William Greenhalf and Bernd Holleczek and Cornelia Schroeder and Ben Sch{\"o}ttker and Audrius Ivanauskas and Laura Ginocchi and Key, {Timothy J} and P{\'e}ter Hegyi and Livia Archibugi and Erika Darvasi and Daniela Basso and Cosimo Sperti and Bijlsma, {Maarten F} and Orazio Palmieri and Viktor Hlavac and Renata Talar-Wojnarowska and Beatrice Mohelnikova-Duchonova and Thilo Hackert and Yogesh Vashist and Ondrej Strouhal and {van Laarhoven}, Hanneke and Francesca Tavano and Martin Lovecek and Christos Dervenis and Ferenc Izb{\'e}ki and Andrea Padoan and Ewa Ma{\l}ecka-Panas and Evaristo Maiello and Giuseppe Vanella and Gabriele Capurso and Izbicki, {Jakob R} and Theodoropoulos, {George E} and Krzysztof Jamroziak and Verena Katzke and Rudolf Kaaks and Andrea Mambrini and Papanikolaou, {Ioannis S} and Rich{\'a}rd Szmola and Andrea Szentesi and Juozas Kupcinskas and Simona Bursi and Eithne Costello and Ugo Boggi and Milanetto, {Anna Caterina} and Stefano Landi and Maria Gazouli and Ludmila Vodickova and Pavel Soucek and Domenica Gioffreda and Federica Gemignani and Hermann Brenner and Oliver Strobel and Markus B{\"u}chler and Pavel Vodicka and Salvatore Paiella and Federico Canzian and Daniele Campa",
note = "{\textcopyright} Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.",
year = "2021",
month = jun,
doi = "10.1136/jmedgenet-2020-106961",
language = "English",
volume = "58",
pages = "369--377",
journal = "J MED GENET",
issn = "0022-2593",
publisher = "BMJ PUBLISHING GROUP",
number = "6",

}

RIS

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 -