Lazzari Grazia, Natalicchio Maria Iole, Terlizzi Angela, Perri Francesco, Silvano Giovanni
Radiation Oncology Unit, San Giuseppe Moscati Hospital, Taranto.
Molecular Biology Laboratory, Pathological Anatomy Department, Ospedali Riuniti, Foggia.
Breast Cancer (Dove Med Press). 2017 May 29;9:401-406. doi: 10.2147/BCTT.S136048. eCollection 2017.
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 () and (), respectively, homozygous for A313G (G/G) mutation in glutathione S transferase Pi 1 (), and wild-type for A4541G (A/A) in and G135C (G/G) in 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.
近来，人们对正常组织和肿瘤对放疗（RT）的个体间差异产生了浓厚兴趣，因为组织放射敏感性似乎受基因控制。越来越多的证据表明，多态性基因变异，如单核苷酸多态性（SNP），可能影响放疗后正常组织的反应。研究最多的SNP包括参与DNA修复（单链和双链断裂以及碱基切除）的基因中的SNP，以及对氧化应激有反应的基因中的SNP。
我们报告了一名60岁早期乳腺癌女性的病例，该患者接受了辅助激素治疗和传统放疗，随后出现了照射乳房不可接受的美容毒性，需要对参与DNA修复机制的基因进行基因检测。结果发现，该患者在X射线修复交叉互补基因1（XRCC1）中的G28152A（T/C）和C18067T（A/G）突变分别为杂合子，在谷胱甘肽S转移酶Pi 1（GSTP1）中的A313G（G/G）突变为纯合子，在XRCC3中的A4541G（A/A）和在RAD51重组酶中的G135C（G/G）为野生型。
当放疗后正常组织出现严重现象时，应考虑SNP的作用，因为了解个体放射敏感性的分子基础可能有助于识别可能需要定制治疗策略的中度或极度放射敏感患者。
