A genome-wide association study on radiation induced fibrosis in breast cancer patients

Radiation-induced fibrosis affects women having undergone post-lumpectomy radiotherapy to a varying degree and remains a significant late morbidity for breast cancer patients. While Single Nucleotide Polymorphisms (SNPs) have been linked to fibrosis after radiotherapy (RT), the genetic architecture remains incompletely understood. We aimed to identify new genetic variants in a cohort of early breast cancer patients representing two cohorts treated within the Danish Breast Cancer Group (DBCG) protocols.

A genome-wide association study (GWAS) was conducted on 869 patients treated with lumpectomy and adjuvant radiotherapy within the DBCG trials hypo- versus normofractionated radiotherapy trial, DBCG-HYPO, and the DBCG partial versus whole breast irradiation trial, DBCG-PBI. After genotyping and imputation, we tested associations between common variants and grade 2-3 fibrosis (LENT-SOMA) using a per-risk allele log-additive model. The threshold for genome-wide significance was set at P < 5 × 10^-8.

After adjusting for principal component outliers, we identified a suggestive association on chromosome 10 (P = 5.90 × 10^-8). The lead variant was rs75542274. While this locus approached the pre-defined genome-wide significance threshold, no other variants reached significance.

This exploratory GWAS identified a potential susceptibility locus for radiation-induced fibrosis on chromosome 10. Given the near-significant nature of this finding, independent validation or meta-analysis is required to confirm the role of rs75542274 in the development of RT-induced fibrosis. Further analysis is warranted.