Vorarlberg Institute for Vascular Investigation and Treatment, 6800 Feldkirch, Austria; Private University of the Principality of Liechtenstein, 9495 Triesen, Liechtenstein.
Department of Obstetrics and Gynecology, Innsbruck Medical University, 6020 Innsbruck, Austria.
Eur J Cancer. 2014 Aug;50(12):2134-41. doi: 10.1016/j.ejca.2014.05.007. Epub 2014 Jun 5.
Deregulation of hepatocyte growth factor (HGF)/mesenchymal-epithelial transition factor (MET) signalling has been associated with poor clinical outcome in breast cancer and other cancers. The recently discovered metastasis-associated in colon cancer-1 (MACC1) gene is a key regulator of the HGF/MET pathway. Potential links between genetic variants of the MACC1 gene and survival in breast cancer patients are unknown. In the present study, we therefore aimed to investigate the influence of MACC1 polymorphisms on event-free and overall survival in patients with human epidermal growth factor 2 (HER2)-positive breast cancer.
The present study included 164 consecutive white patients with HER2-positive breast cancer. Three MACC1 polymorphisms, rs1990172, rs975263 and rs3735615, already associated with cancer prognosis or with potential functional effects, were genotyped by the 5' nuclease assay.
Multivariate Cox regression analysis adjusted for age and tumour stage showed increased risk for progression or death for carriers of the rare allele (G-allele) of single nucleotide polymorphism (SNP) rs1990172 (hazard ratios (HR) = 2.26; p = 0.004 and HR = 3.13; p = 0.001 for event-free survival and overall survival, respectively). In addition, we were able to demonstrate an adverse effect on cancer prognosis for carriers of the rare allele (T-allele) of SNP rs975263 (HR = 2.17; p = 0.007 and HR = 2.80; p = 0.003 for event-free survival and overall survival, respectively). The rare allele (C-allele) of SNP rs3735615 showed a significant protective impact on event-free survival as well as overall survival (HR = 0.25; p = 0.001, and HR = 0.16; p = 0.001, respectively).
This study provides first evidence that MACC1 polymorphisms are associated with clinical outcome for HER2-positive breast cancer patients. Further studies are warranted to validate these findings.
肝细胞生长因子（HGF）/间质上皮转化因子（MET）信号的失调与乳腺癌和其他癌症的不良临床结局有关。最近发现的结肠癌转移相关基因 1（MACC1）是 HGF/MET 通路的关键调节因子。MACC1 基因的遗传变异与乳腺癌患者生存之间的潜在联系尚不清楚。在本研究中，我们旨在研究 MACC1 多态性对人表皮生长因子 2（HER2）阳性乳腺癌患者无事件生存和总生存的影响。
本研究纳入了 164 例连续的 HER2 阳性乳腺癌白种人患者。通过 5' 核酸酶分析，对与癌症预后相关或具有潜在功能影响的 3 个 MACC1 多态性(rs1990172、rs975263 和 rs3735615)进行基因分型。
多变量 Cox 回归分析调整年龄和肿瘤分期后显示，单核苷酸多态性（SNP）rs1990172 罕见等位基因（G 等位基因）携带者发生进展或死亡的风险增加（无事件生存和总生存的风险比（HR）分别为 2.26；p = 0.004 和 HR = 3.13；p = 0.001）。此外，我们还能够证明 SNP rs975263 罕见等位基因（T 等位基因）携带者对癌症预后有不良影响（无事件生存和总生存的 HR 分别为 2.17；p = 0.007 和 HR = 2.80；p = 0.003）。SNP rs3735615 的罕见等位基因（C 等位基因）对无事件生存和总生存均有显著的保护作用（HR = 0.25；p = 0.001 和 HR = 0.16；p = 0.001）。
本研究首次提供了 MACC1 多态性与 HER2 阳性乳腺癌患者临床结局相关的证据。需要进一步的研究来验证这些发现。
