Castro E, Olmos D, Garcia A, Cruz J J, González-Sarmiento R
Department of Medical Oncology, Hospital Universitario de Salamanca, Paseo San Vicente, CP 37007, Salamanca, Spain,
Clin Transl Oncol. 2014 Feb;16(2):158-65. doi: 10.1007/s12094-013-1055-8. Epub 2013 Jun 6.
Anthracyclines have various mechanisms of action that in the end lead to DNA double-strand breaks. Single-nucleotide polymorphisms (SNPs) in DNA repair genes may alter the protein function, affecting DNA repair proficiency and, therefore, the efficiency of DNA damaging chemotherapy. We have analysed whether SNPs in DNA repair genes (XRCC1, XRCC3 and XPD) could be useful to predict the response to anthracyclines in patients with early-stage breast cancer (EBC).
Peripheral blood samples from 150 patients with EBC were used for genotyping XRCC3Thr241Met, XRCC1Arg399Gln and XPDLys751Gln. Genotypes were correlated with survival outcomes.
Eighty-four patients received treatment with chemotherapy regimens containing anthracyclines. In this group, patients with XRCC1Arg399Arg had a significant improvement in 5-year Disease Free Survival (DFS) compared with those with the Arg/Gln and Gln/Gln variants (84 vs 46 %, p = 0.026). In the multivariate analysis, XRCC1Arg399Arg was reported as an independent prognostic factor for DFS (HR 0.4, CI-95 % 0.2-0.9, p = 0.035). Patients with the XRCC3 Met241Met genotype presented better 5-year OS than those carrying the Thr/Thr and Met/Thr variants (100 vs 70 %, p = 0.030). A multivariate analysis for OS confirmed the independent prognostic value of XRCC3 Met241Met (HR 0.15, CI-95 % 0.02-0.90, p = 0.048). These differences were not significant when patients receiving other chemotherapy treatments, different from anthracyclines, were also considered (n = 150). XPDLys751Lys was associated with older age at diagnosis than the Lys/Gln and Gln/Gln genotypes (65 vs 58 years, p < 0.0001).
XRCC3Thr241Met and XRCC1Arg399Gln may be predictive of survival outcome in EBC patients treated with anthracycline-based chemotherapy regimens.
蒽环类药物具有多种作用机制，最终会导致DNA双链断裂。DNA修复基因中的单核苷酸多态性（SNP）可能会改变蛋白质功能，影响DNA修复能力，进而影响DNA损伤化疗的效果。我们分析了DNA修复基因（XRCC1、XRCC3和XPD）中的SNP是否有助于预测早期乳腺癌（EBC）患者对蒽环类药物的反应。
采用150例EBC患者的外周血样本对XRCC3Thr241Met、XRCC1Arg399Gln和XPDLys751Gln进行基因分型。将基因型与生存结果进行关联分析。
84例患者接受了含蒽环类药物的化疗方案治疗。在该组中，与携带Arg/Gln和Gln/Gln变异的患者相比，携带XRCC1Arg399Arg的患者5年无病生存率（DFS）有显著提高（84%对46%，p = 0.026）。在多变量分析中，XRCC1Arg399Arg被报告为DFS的独立预后因素（风险比0.4，95%置信区间0.2 - 0.9，p = 0.035）。携带XRCC3 Met241Met基因型的患者5年总生存率（OS）高于携带Thr/Thr和Met/Thr变异的患者（100%对70%，p = 0.030）。OS的多变量分析证实了XRCC3 Met241Met的独立预后价值（风险比0.15，95%置信区间0.02 - 0.90，p = 0.048）。当考虑接受不同于蒽环类药物的其他化疗治疗的患者时（n = 150），这些差异不显著。XPDLys751Lys与诊断时年龄较大相关，高于Lys/Gln和Gln/Gln基因型（65岁对58岁，p < 0.0001）。
XRCC3Thr241Met和XRCC1Arg399Gln可能预测接受蒽环类药物化疗方案治疗的EBC患者的生存结果。
