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@ARTICLE{RaresFranco:168332,
author = {N. Rares Franco and M. Carlotta Massi and F. Ieva and A.
Manzoni and A. Maria Paganoni and P. Zunino and L. Veldeman
and P. Ost and V. Fonteyne and C. J. Talbot and T. Rattay
and A. Webb and K. Johnson and M. Lambrecht and K.
Haustermans and G. De Meerleer and D. de Ruysscher and B.
Vanneste and E. Van Limbergen and A. Choudhury and R. M.
Elliott and E. Sperk and M. Veldwijk and C. Herskind and B.
Avuzzi and B. Noris Chiorda and R. Valdagni and D. Azria and
M.-P. Farcy-Jacquet and M. Brengues and B. S. Rosenstein and
R. G. Stock and A. Vega and M. Elías Aguado-Barrera and P.
Sosa-Fajardo and A. M. Dunning and L. Fachal and S. L. Kerns
and D. Payne and J. Chang-Claude$^*$ and P. Seibold$^*$ and
C. Ml West and T. Rancati and Y. Lievens and M. van Eijkeren
and C. Monten and W. De Neve and S. Peeters and C. Weltens
and G. Defraene and E. van Limberghen and E. Briers and C.
Bourgier and R. Draghici and F. Bons and T. Blaschke and C.
Weiß and I. Helmbold and C. Weißenberger and P. Stegmaier
and J. Claßen and U. Giesche and M.-L. Sautter-Bihl and B.
Neu and T. Schnabel and M. Ehmann and B. Gauter-Fleckenstein
and J. Schäfer and T. Giandini and M. Franceschini and C.
Sangalli and S. Morlino and L. Lozza and M. C. De Santis and
G. Pietro and E. Delmastro and E. Garibaldi and A. Cicchetti
and B. Piqué-Leiva and M. Molla and A. Giraldo and M. Ramos
and R. Lobato-Busto and L. Torrado Moya and I.
Dominguez-Rios and I. Fajardo-Paneque and P. Calvo-Crespo
and A. Carballo and P. Peleteiro and Olivia-Fuentes-Rios and
A. Gomez-Caamano and V. Harrop and D. Payne and M. Keni and
P. R. Symonds and S. Lavers and S. Wright and S. Thiagarajan
and L. Aznar-Garcia and K. Kancherla and C. Kent and S.
Vasanthan and D. Appleton and M. Kaushik and F. Kenny and H.
Khout and J. Krupa and K. V. Lambert and S. Pilgrim and S.
Shokuhi and K. Valassiadou and I. Bioangiu and K. Sampson
and A. Osman and C. Faivre-Finn and K. Foweraker and A.
Pascoe and C. P. Esler and T. Ward and D. S. Higginson and
S. Green},
collaboration = {R. Consortium},
title = {{D}evelopment of a method for generating {SNP}
interaction-aware polygenic risk scores for radiotherapy
toxicity.},
journal = {Radiotherapy and oncology},
volume = {159},
issn = {0167-8140},
address = {Amsterdam [u.a.]},
publisher = {Elsevier Science},
reportid = {DKFZ-2021-00835},
pages = {241-248},
year = {2021},
note = {2021 Apr 8;159:241-248},
abstract = {To identify the effect of single nucleotide polymorphism
(SNP) interactions on the risk of toxicity following
radiotherapy (RT) for prostate cancer (PCa) and propose a
new method for polygenic risk score incorporating SNP-SNP
interactions (PRSi).Analysis included the REQUITE PCa cohort
that received external beam RT and was followed for 2 years.
Late toxicity endpoints were: rectal bleeding, urinary
frequency, haematuria, nocturia, decreased urinary stream.
Among 43 literature-identified SNPs, the $30\%$ most
strongly associated with each toxicity were tested. SNP-SNP
combinations (named SNP-allele sets) seen in $≥10\%$ of
the cohort were condensed into risk (RS) and protection (PS)
scores, respectively indicating increased or decreased
toxicity risk. Performance of RS and PS was evaluated by
logistic regression. RS and PS were then combined into a
single PRSi evaluated by area under the receiver operating
characteristic curve (AUC).Among 1,387 analysed patients,
toxicity rates were $11.7\%$ (rectal bleeding), $4.0\%$
(urinary frequency), $5.5\%$ (haematuria), $7.8\%$
(nocturia) and $17.1\%$ (decreased urinary stream). RS and
PS combined 8 to 15 different SNP-allele sets, depending on
the toxicity endpoint. Distributions of PRSi differed
significantly in patients with/without toxicity with AUCs
ranging from 0.61 to 0.78. PRSi was better than the
classical summed PRS, particularly for the urinary
frequency, haematuria and decreased urinary stream
endpoints.Our method incorporates SNP-SNP interactions when
calculating PRS for radiotherapy toxicity. Our approach is
better than classical summation in discriminating patients
with toxicity and should enable incorporating genetic
information to improve normal tissue complication
probability models.},
keywords = {SNPs (Other) / epistasis (Other) / genetic risk factors
(Other) / late toxicity (Other) / prostate cancer (Other) /
radiotherapy (Other)},
cin = {C020},
ddc = {610},
cid = {I:(DE-He78)C020-20160331},
pnm = {313 - Krebsrisikofaktoren und Prävention (POF4-313)},
pid = {G:(DE-HGF)POF4-313},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:33838170},
doi = {10.1016/j.radonc.2021.03.024},
url = {https://inrepo02.dkfz.de/record/168332},
}