Söderlund Leifler K, Asklid A, Fornander T, Stenmark Askmalm M
Division of Surgery and Clinical Oncology, Department of Clinical and Experimental Medicine, Linköping University, 581 85, Linköping, Sweden.
J Cancer Res Clin Oncol. 2015 May;141(5):797-804. doi: 10.1007/s00432-014-1859-0. Epub 2014 Oct 30.
RAD51, a central player in the response to DNA damage, has been suspected to contribute to tumour resistance to therapy. A single-nucleotide polymorphism, RAD51 135G>C, in the untranslated region of the RAD51 gene elevates breast cancer risk among BRCA2 carriers. In this study, it was investigated whether this polymorphism is related to prognosis of breast cancer and RAD51 protein expression and whether it is indicative of resistance to radiotherapy or cyclophosphamide/methotrexate/5-fluorouracil (CMF) chemotherapy.
We genotyped 306 patients with early breast cancer, who were randomised to receive post-operative radiotherapy or CMF chemotherapy, for the RAD51 135G>C polymorphism. RAD51 protein expression was evaluated with immunohistochemistry.
15.4 % of the patients had at least one C-allele (three were C homozygotes). There was no correlation between genotype and protein expression. Patients who were G homozygotes benefitted from radiotherapy with decreased risk of local recurrences (RR = 0.32, 95 % C.I. 0.16-0.64, p = 0.001). CMF chemotherapy reduced the risk of distant recurrence for patients carrying at least one C-allele (RR = 0.29, 95 % C.I. 0.10-0.88, p = 0.03), whereas G homozygotes had no benefit from chemotherapy. There was a significant interaction between chemotherapy and genotype (p = 0.02).
The results suggest that the RAD51 135G>C polymorphism predicts CMF chemotherapy effect in early breast cancer.
RAD51是DNA损伤反应中的关键因子，一直被怀疑与肿瘤的治疗抵抗有关。RAD51基因非翻译区的单核苷酸多态性RAD51 135G>C会增加BRCA2携带者患乳腺癌的风险。本研究旨在探讨该多态性是否与乳腺癌预后、RAD51蛋白表达相关，以及是否可指示对放疗或环磷酰胺/甲氨蝶呤/5-氟尿嘧啶（CMF）化疗的抵抗性。
我们对306例早期乳腺癌患者进行基因分型，检测RAD51 135G>C多态性，这些患者被随机分配接受术后放疗或CMF化疗。采用免疫组织化学法评估RAD51蛋白表达。
15.4%的患者至少携带一个C等位基因（3例为C纯合子）。基因型与蛋白表达之间无相关性。G纯合子患者从放疗中获益，局部复发风险降低（RR = 0.32，95%置信区间0.16 - 0.64，p = 0.001）。CMF化疗降低了至少携带一个C等位基因患者的远处复发风险（RR = 0.29，95%置信区间0.10 - 0.88，p = 0.03），而G纯合子患者未从化疗中获益。化疗与基因型之间存在显著交互作用（p = 0.02）。
结果表明，RAD51 135G>C多态性可预测早期乳腺癌患者对CMF化疗的疗效。
