TY  - JOUR
AU  - Jandu, Harkeran K
AU  - Veal, Colin D
AU  - Fachal, Laura
AU  - Luccarini, Craig
AU  - Aguado-Barrera, Miguel E
AU  - Altabas, Manuel
AU  - Azria, David
AU  - Baten, Adinda
AU  - Bourgier, Celine
AU  - Bultijnck, Renée
AU  - Colciago, Riccardo R
AU  - Farcy-Jacquet, Marie-Pierre
AU  - Chang-Claude, Jenny
AU  - Choudhury, Ananya
AU  - Dunning, Alison
AU  - Elliott, Rebecca M
AU  - Green, Sheryl
AU  - Gutiérrez-Enríquez, Sara
AU  - Herskind, Carsten
AU  - Lambrecht, Maarten
AU  - Monten, Christel
AU  - Rancati, Tiziana
AU  - Reyes, Victoria
AU  - Rosenstein, Barry S
AU  - De Ruysscher, Dirk
AU  - Carmen De Santis, Maria
AU  - Seibold, Petra
AU  - Sperk, Elena
AU  - Veldwijk, Marlon
AU  - Paul Symonds, R.
AU  - Stobart, Hilary
AU  - Taboada-Valladares, Begoña
AU  - Vega, Ana
AU  - Veldeman, Liv
AU  - Webb, Adam J
AU  - Weltens, Caroline
AU  - West, Catharine M
AU  - Rattay, Tim
AU  - Talbot, Christopher J
TI  - Genome-wide association study of treatment-related toxicity two years following radiotherapy for breast cancer.
JO  - Radiotherapy and oncology
VL  - 187
SN  - 0167-8140
CY  - Amsterdam [u.a.]
PB  - Elsevier Science
M1  - DKFZ-2023-01395
SP  - 109806
PY  - 2023
N1  - Volume 187, October 2023, 109806Radiotherapy and Oncology
AB  - 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 x 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 x 10-8), breast oedema grade≥2 with rs12657177 (p=1.12 x 10-10), rs75912034 (p= 1.12 x 10-10), rs145328458 (p=1.06 x 10-9) and rs61966612 (p=1.23 x 10-9), induration grade≥2 with rs77311050 (p=2.54 x 10-8) and rs34063419 (p=1.21 × 10-8), and arm lymphoedema grade≥1 with rs643644 (p=3.54 x 10-8). Heritability estimates across different endpoints ranged from 25
KW  - Breast Cancer (Other)
KW  - Genome-wide association study (Other)
KW  - Late radiotherapy side effects (Other)
KW  - Radiogenomics (Other)
KW  - Radiotherapy (Other)
KW  - late toxicity (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:37437607
DO  - DOI:10.1016/j.radonc.2023.109806
UR  - https://inrepo02.dkfz.de/record/277474
ER  -