Su Yonghui, Jiang Yongdong, Sun Shanshan, Yin Huizi, Shan Ming, Tao Weiyang, Ge Xiaofeng, Pang Da
Department of Breast Surgery, The Affiliated Tumor Hospital of Harbin Medical University, Harbin 150081, China.
Department of Radiotherapy, The Affiliated Tumor Hospital of Harbin Medical University, Harbin 150081, China.
Cancer Epidemiol. 2015 Dec;39(6):1123-7. doi: 10.1016/j.canep.2015.08.011. Epub 2015 Aug 29.
HER2 protein expression has been considered to be an important prognostic factor in breast cancer patients. Although the molecular mechanism of HER2 protein expression is currently unknown, single nucleotide polymorphisms (SNPs) of the HER2 gene may have some effects on its own expression. Here, we performed a trial to study the association between HER2 genetic polymorphisms and its protein expression in breast cancer.
Three SNPs in the HER2 gene were genotyped in 303 breast cancer patients using the Sequenom Mass ARRAY system. HER2 protein expression, ER, PR, P53, and Ki67 status was detected by immunohistochemistry. A Pearson's chi-square test was used to analyze the associations of the polymorphisms with its protein expression, corresponding with clinicopathological characteristics of breast cancer.
Under the codominant model, rs1058808 and rs2517956 polymorphisms were associated with HER2 protein expression in breast cancer (p=0.007; p=0.008, respectively). For SNP rs1058808, patients with genotypes CG and GG were more likely to have high HER2 protein expression than patients with genotype CC (p=0.007). No significant associations could be found between the three SNPs and breast cancer patients' clinical stage, tumor size, histological grade, lymph node metastasis, ER, PR, Ki67 and P53 status (p>0.05).
HER2 rs1058808 and rs2517956 polymorphisms are associated with its protein expression in breast cancer. Our study might provide new insights into the mechanisms of HER2 protein expression.
HER2蛋白表达被认为是乳腺癌患者的一个重要预后因素。尽管目前HER2蛋白表达的分子机制尚不清楚，但HER2基因的单核苷酸多态性（SNP）可能对其自身表达有一定影响。在此，我们进行了一项试验，以研究HER2基因多态性与其在乳腺癌中蛋白表达之间的关联。
使用Sequenom Mass ARRAY系统对303例乳腺癌患者的HER2基因中的三个SNP进行基因分型。通过免疫组织化学检测HER2蛋白表达、雌激素受体（ER）、孕激素受体（PR）、P53和Ki67状态。采用Pearson卡方检验分析多态性与其蛋白表达的关联，以及与乳腺癌临床病理特征的相关性。
在共显性模型下，rs1058808和rs²517956多态性与乳腺癌中的HER2蛋白表达相关（分别为p = 0.007；p = 0.008）。对于SNP rs1058808，基因型为CG和GG的患者比基因型为CC的患者更有可能具有高HER2蛋白表达（p = 0.007）。在这三个SNP与乳腺癌患者的临床分期、肿瘤大小、组织学分级、淋巴结转移、ER、PR、Ki67和P53状态之间未发现显著关联（p>0.05）。
HER2基因的rs1058808和rs2517956多态性与其在乳腺癌中的蛋白表达相关。我们的研究可能为HER2蛋白表达的机制提供新的见解。
