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Background Radiotherapy-associated secondary cancer is an important issue for the treatment of breast cancer (BCa). This study aimed to investigate the molecular mechanism and genetic risk factors for radiation-associated secondary diseases in BCa. Methods The differentially expressed genes (DEGs) between preradiation and postradiation BCa samples in the GSE65505 dataset were obtained. The pathways related to the radiation-associated DEGs in the protein–protein interaction (PPI) network modules were identified. miRNAs targeted to the key genes in the PPI network were identified, and their association with BCa prognosis was analyzed. Results A total of 136 radiation-associated DEGs preradiation and postradiation BCa samples were screened out. The PPI network consisted of a significant module that consisted of 21 upregulated DEGs that were associated with “hsa04512: ECM–receptor interaction,” “hsa04151: PI3K-Akt signaling pathway,” and “hsa04115: p53 signaling pathway.” Sixteen DEGs, including three collagen genes collagen type I alpha 1 chain ( COL1A1 ),  COL3A1 , and  COL1A2 , were enriched in 17 radiation-associated pathways. The three genes were upregulated in BCa tissues compared with controls and were also elevated by radiation. They were targeted by  hsa - miR - 29a / c , and the expression levels of  hsa - miR - 29a / c  were associated with a poor prognosis of BCa. Conclusions The upregulation of  COL1A1 ,  COL3A1 , and  COL1A2  might be genetic risk factors for radiation-associated secondary diseases in BCa.

Radiation increases COL1A1, COL3A1, and COL1A2 expression in breast cancer