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Development of a method for generating SNP interaction-aware polygenic risk scores for radiotherapy toxicity

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Development of a method for generating SNP interaction-aware polygenic risk scores for radiotherapy toxicity. / Franco, Nicola Rares; Massi, Michela Carlotta; Ieva, Francesca; Manzoni, Andrea; Paganoni, Anna Maria; Zunino, Paolo; Veldeman, Liv; Ost, Piet; Fonteyne, Valérie; Talbot, Christopher J; Rattay, Tim; Webb, Adam; Johnson, Kerstie; Lambrecht, Maarten; Haustermans, Karin; De Meerleer, Gert; de Ruysscher, Dirk; Vanneste, Ben; Van Limbergen, Evert; Choudhury, Ananya; Elliott, Rebecca M; Sperk, Elena; Veldwijk, Marlon R; Herskind, Carsten; Avuzzi, Barbara; Noris Chiorda, Barbara; Valdagni, Riccardo; Azria, David; Farcy-Jacquet, Marie-Pierre; Brengues, Muriel; Rosenstein, Barry S; Stock, Richard G; Vega, Ana; Aguado-Barrera, Miguel E; Sosa-Fajardo, Paloma; Dunning, Alison M; Fachal, Laura; Kerns, Sarah L; Payne, Debbie; Chang-Claude, Jenny; Seibold, Petra; West, Catharine M L; Rancati, Tiziana; REQUITE Consortium.

in: RADIOTHER ONCOL, Jahrgang 159, 06.2021, S. 241-248.

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

Harvard

Franco, NR, Massi, MC, Ieva, F, Manzoni, A, Paganoni, AM, Zunino, P, Veldeman, L, Ost, P, Fonteyne, V, Talbot, CJ, Rattay, T, Webb, A, Johnson, K, Lambrecht, M, Haustermans, K, De Meerleer, G, de Ruysscher, D, Vanneste, B, Van Limbergen, E, Choudhury, A, Elliott, RM, Sperk, E, Veldwijk, MR, Herskind, C, Avuzzi, B, Noris Chiorda, B, Valdagni, R, Azria, D, Farcy-Jacquet, M-P, Brengues, M, Rosenstein, BS, Stock, RG, Vega, A, Aguado-Barrera, ME, Sosa-Fajardo, P, Dunning, AM, Fachal, L, Kerns, SL, Payne, D, Chang-Claude, J, Seibold, P, West, CML, Rancati, T & REQUITE Consortium 2021, 'Development of a method for generating SNP interaction-aware polygenic risk scores for radiotherapy toxicity', RADIOTHER ONCOL, Jg. 159, S. 241-248. https://doi.org/10.1016/j.radonc.2021.03.024

APA

Franco, N. R., Massi, M. C., Ieva, F., Manzoni, A., Paganoni, A. M., Zunino, P., Veldeman, L., Ost, P., Fonteyne, V., Talbot, C. J., Rattay, T., Webb, A., Johnson, K., Lambrecht, M., Haustermans, K., De Meerleer, G., de Ruysscher, D., Vanneste, B., Van Limbergen, E., ... REQUITE Consortium (2021). Development of a method for generating SNP interaction-aware polygenic risk scores for radiotherapy toxicity. RADIOTHER ONCOL, 159, 241-248. https://doi.org/10.1016/j.radonc.2021.03.024

Vancouver

Franco NR, Massi MC, Ieva F, Manzoni A, Paganoni AM, Zunino P et al. Development of a method for generating SNP interaction-aware polygenic risk scores for radiotherapy toxicity. RADIOTHER ONCOL. 2021 Jun;159:241-248. https://doi.org/10.1016/j.radonc.2021.03.024

Bibtex

@article{0e33b7dc2d89448097aa6c05a1e67cf5,
title = "Development of a method for generating SNP interaction-aware polygenic risk scores for radiotherapy toxicity",
abstract = "AIM: 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).MATERIALS AND METHODS: 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).RESULTS: 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.CONCLUSIONS: 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.",
author = "Franco, {Nicola Rares} and Massi, {Michela Carlotta} and Francesca Ieva and Andrea Manzoni and Paganoni, {Anna Maria} and Paolo Zunino and Liv Veldeman and Piet Ost and Val{\'e}rie Fonteyne and Talbot, {Christopher J} and Tim Rattay and Adam Webb and Kerstie Johnson and Maarten Lambrecht and Karin Haustermans and {De Meerleer}, Gert and {de Ruysscher}, Dirk and Ben Vanneste and {Van Limbergen}, Evert and Ananya Choudhury and Elliott, {Rebecca M} and Elena Sperk and Veldwijk, {Marlon R} and Carsten Herskind and Barbara Avuzzi and {Noris Chiorda}, Barbara and Riccardo Valdagni and David Azria and Marie-Pierre Farcy-Jacquet and Muriel Brengues and Rosenstein, {Barry S} and Stock, {Richard G} and Ana Vega and Aguado-Barrera, {Miguel E} and Paloma Sosa-Fajardo and Dunning, {Alison M} and Laura Fachal and Kerns, {Sarah L} and Debbie Payne and Jenny Chang-Claude and Petra Seibold and West, {Catharine M L} and Tiziana Rancati and {REQUITE Consortium}",
note = "Copyright {\textcopyright} 2021 The Authors. Published by Elsevier B.V. All rights reserved.",
year = "2021",
month = jun,
doi = "10.1016/j.radonc.2021.03.024",
language = "English",
volume = "159",
pages = "241--248",
journal = "RADIOTHER ONCOL",
issn = "0167-8140",
publisher = "Elsevier Ireland Ltd",

}

RIS

TY - JOUR

T1 - Development of a method for generating SNP interaction-aware polygenic risk scores for radiotherapy toxicity

AU - Franco, Nicola Rares

AU - Massi, Michela Carlotta

AU - Ieva, Francesca

AU - Manzoni, Andrea

AU - Paganoni, Anna Maria

AU - Zunino, Paolo

AU - Veldeman, Liv

AU - Ost, Piet

AU - Fonteyne, Valérie

AU - Talbot, Christopher J

AU - Rattay, Tim

AU - Webb, Adam

AU - Johnson, Kerstie

AU - Lambrecht, Maarten

AU - Haustermans, Karin

AU - De Meerleer, Gert

AU - de Ruysscher, Dirk

AU - Vanneste, Ben

AU - Van Limbergen, Evert

AU - Choudhury, Ananya

AU - Elliott, Rebecca M

AU - Sperk, Elena

AU - Veldwijk, Marlon R

AU - Herskind, Carsten

AU - Avuzzi, Barbara

AU - Noris Chiorda, Barbara

AU - Valdagni, Riccardo

AU - Azria, David

AU - Farcy-Jacquet, Marie-Pierre

AU - Brengues, Muriel

AU - Rosenstein, Barry S

AU - Stock, Richard G

AU - Vega, Ana

AU - Aguado-Barrera, Miguel E

AU - Sosa-Fajardo, Paloma

AU - Dunning, Alison M

AU - Fachal, Laura

AU - Kerns, Sarah L

AU - Payne, Debbie

AU - Chang-Claude, Jenny

AU - Seibold, Petra

AU - West, Catharine M L

AU - Rancati, Tiziana

AU - REQUITE Consortium

N1 - Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.

PY - 2021/6

Y1 - 2021/6

N2 - AIM: 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).MATERIALS AND METHODS: 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).RESULTS: 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.CONCLUSIONS: 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.

AB - AIM: 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).MATERIALS AND METHODS: 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).RESULTS: 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.CONCLUSIONS: 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.

U2 - 10.1016/j.radonc.2021.03.024

DO - 10.1016/j.radonc.2021.03.024

M3 - SCORING: Journal article

C2 - 33838170

VL - 159

SP - 241

EP - 248

JO - RADIOTHER ONCOL

JF - RADIOTHER ONCOL

SN - 0167-8140

ER -