Grazia Lazzari, Maria Iole Natalicchio, Angela Terlizzi, Francesco Perri, Giovanni Silvano

There has recently been a strong interest in the inter-individual variation in normal tissue and tumor response to radiotherapy (RT), because tissue radiosensitivity seems to be under genetic control. Evidence is accumulating on the role of polymorphic genetic variants, such as single nucleotide polymorphisms (SNPs) that could influence normal tissue response after radiation. The most studied SNPs include those in genes involved in DNA repair (single- and double-strand breaks, and base excision) and those active in the response to oxidative stress. We present the case report of a 60-year-old woman with early breast cancer who underwent adjuvant hormone therapy and conventional radiotherapy, and subsequently developed unacceptable cosmetic toxicities of the irradiated breast requiring a genetic test of genes involved in DNA repair mechanisms. The patient was found to be heterozygous for G28152A (T/C) and C18067T (A/G) mutations in X-ray repair cross-complementing group 1 (XRCC1) and 3 (XRCC3), respectively, homozygous for A313G (G/G) mutation in glutathione S transferase Pi 1 (GSTP1), and wild-type for A4541G (A/A) in XRCC3 and G135C (G/G) in RAD51 recombinase. The role of SNPs should be taken into account when a severe phenomenon appears in normal tissues after radiation treatment, because understanding the molecular basis of individual radiosensitivity may be useful for identifying moderately or extremely radiosensitive patients who may need tailored therapeutic strategies.