Genome-wide association study of treatment-related toxicity two years following radiotherapy for breast cancer.
Breast Cancer
Chronic toxicity
Genome-wide association study
Radiogenomics
Radiotherapy
Radiotherapy side effects
Journal
Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology
ISSN: 1879-0887
Titre abrégé: Radiother Oncol
Pays: Ireland
ID NLM: 8407192
Informations de publication
Date de publication:
10 2023
10 2023
Historique:
received:
20
03
2023
revised:
04
07
2023
accepted:
06
07
2023
medline:
15
9
2023
pubmed:
13
7
2023
entrez:
12
7
2023
Statut:
ppublish
Résumé
Up to a quarter of breast cancer patients treated by surgery and radiotherapy experience clinically significant toxicity. If patients at high risk of adverse effects could be identified at diagnosis, their treatment could be tailored accordingly. This study was designed to identify common single nucleotide polymorphisms (SNPs) associated with toxicity two years following whole breast radiotherapy. A genome-wide association study (GWAS) was performed in 1,640 breast cancer patients with complete SNP, clinical, treatment and toxicity data, recruited across 18 European and US centres into the prospective REQUITE cohort study. Toxicity data (CTCAE v4.0) were collected at baseline, end of radiotherapy, and annual follow-up. A total of 7,097,340 SNPs were tested for association with the residuals of toxicity endpoints, adjusted for clinical, treatment co-variates and population substructure. Quantile-quantile plots showed more associations with toxicity above the p < 5 × 10 This GWAS for long-term breast radiation toxicity provides further evidence for significant association of common SNPs with distinct toxicity endpoints.
Sections du résumé
BACKGROUND AND PURPOSE
Up to a quarter of breast cancer patients treated by surgery and radiotherapy experience clinically significant toxicity. If patients at high risk of adverse effects could be identified at diagnosis, their treatment could be tailored accordingly. This study was designed to identify common single nucleotide polymorphisms (SNPs) associated with toxicity two years following whole breast radiotherapy.
MATERIALS AND METHODS
A genome-wide association study (GWAS) was performed in 1,640 breast cancer patients with complete SNP, clinical, treatment and toxicity data, recruited across 18 European and US centres into the prospective REQUITE cohort study. Toxicity data (CTCAE v4.0) were collected at baseline, end of radiotherapy, and annual follow-up. A total of 7,097,340 SNPs were tested for association with the residuals of toxicity endpoints, adjusted for clinical, treatment co-variates and population substructure.
RESULTS
Quantile-quantile plots showed more associations with toxicity above the p < 5 × 10
CONCLUSIONS
This GWAS for long-term breast radiation toxicity provides further evidence for significant association of common SNPs with distinct toxicity endpoints.
Identifiants
pubmed: 37437607
pii: S0167-8140(23)00344-4
doi: 10.1016/j.radonc.2023.109806
pii:
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
109806Subventions
Organisme : Wellcome Trust
ID : 218505/Z/19/Z
Pays : United Kingdom
Organisme : Department of Health
ID : CL 2017-11-002
Pays : United Kingdom
Organisme : Department of Health
ID : DRF 2014-07-079
Pays : United Kingdom
Organisme : Cancer Research UK
ID : C1094/A1850
Pays : United Kingdom
Organisme : Cancer Research UK
ID : C147/A25254
Pays : United Kingdom
Informations de copyright
Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.