Palomba Grazia, Atzori Francesco, Budroni Mario, Ombra MariaNeve, Cossu Antonio, Sini MariaCristina, Pusceddu Valeria, Massidda Bruno, Frau Barbara, Notari Francesca, Ionta MariaTeresa, Palmieri Giuseppe
J Transl Med. 2014 Sep 25;12:272. doi: 10.1186/s12967-014-0272-4.
Polymorphisms in the excision repair cross-complimentary group 1 (ERCC1) gene have been involved in the prognosis of various cancers. In the present study, we evaluated the prognostic role of the two most common ERCC1 polymorphisms in patients with T4 breast cancer receiving platinum-based chemotherapy.
A total of 47 patients with T4 breast cancer undergoing treatment with a platinum-based regimen were collected and followed up (median 159 months; range, 42-239 months). ERCC1 C8092A (rs3212986) and T19007C (rs11615) polymorphisms were genotyped, using an automated sequencing approach. The same series was screened for BRCA1/2 mutations by DHPLC analysis and DNA sequencing.
Among the tested patients, 16 (34%) and 25 (53%) presented the 8092A (homo-zygosity A/A or heterozygosity A/C) and the 19007C (homozygosity C/C or heterozygosity C/T) genotypes, respectively. The 8092A and 19007C genotypes in ERCC1 were significantly associated with overall survival in T4 breast cancer patients treated with chemotherapy containing platinum (p-values = 0.036 and 0.004, respectively). Univariate and multivariate Cox regression analyses showed that combination of 8092A and 19007C genotypes acts as a significant prognostic factor in women with T4 breast cancer receiving platinum-based chemotherapy (p-values = 0.022 and 0.049, respectively). Two (4.3%) out of 47 cases were found to carry BRCA1/2 mutations; they presented the highest overall survival rates into the series.
The ERCC1 8092A and 19007C genotypes or their combination may predict a favorable prognosis in T4 breast cancer patients undergoing a platinum-based treatment. Further large-scale, prospective studies are needed to validate our findings.
切除修复交叉互补基因1（ERCC1）的多态性与多种癌症的预后有关。在本研究中，我们评估了ERCC1两个最常见的多态性在接受铂类化疗的T4期乳腺癌患者中的预后作用。
共收集47例接受铂类方案治疗的T4期乳腺癌患者并进行随访（中位随访时间159个月；范围42 - 239个月）。采用自动测序法对ERCC1 C8092A（rs3212986）和T19007C（rs11615）多态性进行基因分型。通过变性高效液相色谱分析（DHPLC）和DNA测序对同一组患者进行BRCA1/2突变筛查。
在检测的患者中，分别有16例（34%）和25例（53%）呈现8092A（纯合子A/A或杂合子A/C）和19007C（纯合子C/C或杂合子C/T）基因型。ERCC1中的8092A和19007C基因型与接受含铂化疗的T4期乳腺癌患者的总生存期显著相关（p值分别为0.036和0.004）。单因素和多因素Cox回归分析显示，8092A和19007C基因型的组合是接受铂类化疗的T4期乳腺癌女性患者的显著预后因素（p值分别为0.022和0.049）。47例病例中有2例（4.3%）被发现携带BRCA1/2突变；他们在该组中总生存率最高。
ERCC1 8092A和19007C基因型或其组合可能预测接受铂类治疗的T4期乳腺癌患者的良好预后。需要进一步进行大规模前瞻性研究来验证我们的发现。
