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@ARTICLE{Galeotti:156769,
author = {A. A. Galeotti and M. Gentiluomo and C. Rizzato$^*$ and O.
M. A. Obazee$^*$ and J. P. Neoptolemos and C. Pasquali and
M. Nentwich and G. M. Cavestro and R. Pezzilli and W.
Greenhalf and B. Holleczek$^*$ and C. Schroeder and B.
Schöttker$^*$ and A. Ivanauskas and L. Ginocchi and T. J.
Key and P. Hegyi and L. Archibugi and E. Darvasi and D.
Basso and C. Sperti and M. F. Bijlsma and O. Palmieri and V.
Hlavac and R. Talar-Wojnarowska and B. Mohelnikova-Duchonova
and T. Hackert and Y. Vashist and O. Strouhal and H. van
Laarhoven and F. Tavano and M. Lovecek and C. Dervenis and
F. Izbéki and A. Padoan and E. Małecka-Panas and E.
Maiello and G. Vanella and G. Capurso and J. R. Izbicki and
G. E. Theodoropoulos and K. Jamroziak and V. Katzke$^*$ and
R. Kaaks$^*$ and A. Mambrini and I. S. Papanikolaou and R.
Szmola and A. Szentesi and J. Kupcinskas and S. Bursi and E.
Costello and U. Boggi and A. C. Milanetto and S. Landi and
M. Gazouli and L. Vodickova and P. Soucek and D. Gioffreda
and F. Gemignani and H. Brenner$^*$ and O. Strobel and M.
Büchler and P. Vodicka and S. Paiella and F. Canzian$^*$
and D. Campa},
title = {{P}olygenic and multifactorial scores for pancreatic ductal
adenocarcinoma risk prediction.},
journal = {Journal of medical genetics},
volume = {58},
number = {6},
issn = {1468-6244},
address = {London},
publisher = {BMJ Publishing Group},
reportid = {DKFZ-2020-01093},
pages = {369-377},
year = {2021},
note = {2021 Jun;58(6):369-377#EA:C055#},
abstract = {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.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.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.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).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.},
cin = {C055 / C070 / C020 / C120 / HD01},
ddc = {610},
cid = {I:(DE-He78)C055-20160331 / I:(DE-He78)C070-20160331 /
I:(DE-He78)C020-20160331 / I:(DE-He78)C120-20160331 /
I:(DE-He78)HD01-20160331},
pnm = {313 - Krebsrisikofaktoren und Prävention (POF4-313)},
pid = {G:(DE-HGF)POF4-313},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:32591343},
doi = {10.1136/jmedgenet-2020-106961},
url = {https://inrepo02.dkfz.de/record/156769},
}