Genome-wide association study of treatment-related toxicity two years following radiotherapy for breast cancer

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 id...

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Detalhes bibliográficos
Autores: Jandu, H.K., Veal, C.D., Fachal Vilar, Laura, Luccarini, C., Aguado-Barrera, M.E., Altabas, M., Azria, D., Baten, A., Bourgier, C., Bultijnck, R., Colciago, R.R., Farcy-Jacquet, M.-P., Chang-Claude, J., Choudhury, A., Dunning, A., Elliott, R.M., Green, S., Gutiérrez-Enríquez, S., Herskind, C., Lambrecht, M., Monten, C., Rancati, T., Reyes, V., Rosenstein, B.S., De Ruysscher, D., Carmen De Santis, M., Seibold, P., Sperk, E., Veldwijk, M., Paul Symonds, R., Stobart, H., Taboada Valladares, Maria Begoña, Vega Gliemmo, Ana, Veldeman, L., Webb, A.J., Weltens, C., West, C.M., Rattay, T., Talbot, C.J.
Formato: artículo
Fecha de publicación:2023
País:España
Recursos:Servizo Galego de Saúde (SERGAS)
Repositorio:RUNA. Repositorio da Consellería de Sanidade e Sergas
OAI Identifier:oai:runa.sergas.gal:20.500.11940/21533
Acesso em linha:https://portalcientifico.sergas.gal//documentos/64f6355566ccc641d10d6b69
http://hdl.handle.net/20.500.11940/21533
Access Level:acceso abierto
Palavra-chave:Humans
Female
Breast Neoplasms
Genome-Wide Association Study
Cohort Studies
Prospective Studies
Radiation Injuries
Polymorphism, Single Nucleotide
FPGMX
AS Santiago
CHUS
Descrição
Resumo: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 × 10-5 level than expected by chance. Eight SNPs reached genome-wide significance. Nipple retraction grade ? 2 was associated with the rs188287402 variant (p = 2.80 × 10-8), breast oedema grade ? 2 with rs12657177 (p = 1.12 × 10-10), rs75912034 (p = 1.12 × 10-10), rs145328458 (p = 1.06 × 10-9) and rs61966612 (p = 1.23 × 10-9), induration grade ? 2 with rs77311050 (p = 2.54 × 10-8) and rs34063419 (p = 1.21 × 10-8), and arm lymphoedema grade ? 1 with rs643644 (p = 3.54 × 10-8). Heritability estimates across significant endpoints ranged from 25% to 39%. Our study did not replicate previously reported SNPs associated with breast radiation toxicity at the pre-specified significance level. Conclusions: This GWAS for long-term breast radiation toxicity provides further evidence for significant association of common SNPs with distinct toxicity endpoints.

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