乳腺癌中HER-2基因多态性与蛋白表达的相关性研究

Association between HER-2 gene polymorphism and protein expression in breast cancer

背景与目的：致病基因的多态性可能会影响该基因的功能，从而引起个体肿瘤易感性的差异和个体内生物活性物质效应的改变。本研究旨在研究HER．2基因多态性与其蛋白表达的关系，并分析其与乳腺癌临床病理特征的相关性。方法：收集303例汉族女性乳腺癌患者为研究对象，运用MassARRAY技术平台检测船R-2基因rs2517954和rs2517955单核苷酸多态性。同时采用免疫组织化学法检测相应乳腺癌组织中HER-2蛋白表达并检测雌激素受体（estrogenreceptor，ER）、孕激素受体（progesteronereceptor，PR）、P53及Ki67表达。以Pearson矿分析这两个位点和其蛋白表达的关系，并分析其与乳腺癌临床病理特征的相关性。结果：在共显性模型下，HER-2基因rs2517954和rs2517955位点多态性与其蛋白表达相关（x2=9．613，P=O．008；x2=9．613，P=O．008）。在显性模型下，HER-2基因rs2517955位点TT纯合突变型和cT杂合突变型的频率与其蛋白表达相关（x2=8．894，P=-O．003）。HER-2基因rs2517954和rs2517955位点多态性与患者的临床分期、肿瘤大小、组织学分级、淋巴结转移、ER、PR、Ki67及P53表达均无显著相关性（P〉0．05）。结论：HER-2基因rs2517955多态性位点与其蛋白表达具有相关性，对该位点进一步研究可能有助于阐明乳腺癌中HER-2蛋白的表达机制。

Background and purpose： Pathogenic gene polymorphism may affect the function of gene, leading to the difference of individual tumor susceptibility and heterogeneity of bioactive substances in individuals. The purpose of this study was to investigate the interrelationship between HER-2 gene polymorphism and its protein expression, and to evaluate their association with the clinicopathological characteristics of breast cancer. Methods： The data from a total number of 303 female breast cancer patients of Han ethnicity were collected. The MassARRAY platform was used to examine HER-2 gene rs2517954 and rs2517955 single nucleotide polymorphisms. Meanwhile immunohistochemistry was used to detect HER-2 protein expression and corresponding estrogen receptor （ER）, progesterone receptor （PR）, P53 and Ki-67 expressions in breast cancer tissues. Pearson chi-square test was used to study the relationship of the two loci and the protein expression, and their correlation with clinicopathological features of breast cancer was analyzed. Results： Under the codominant model, HER-2 gene rs2517954 and rs2517955 loci polymorphisms were associated with its protein expression （Z2=9.613, P=-0.008; Z2=9.613, P=0.008）. And under the dominant model, HER-2 gene rs2517955 loci TT homozygous and CT heterozygous mutant was associated with its protein expression 0f2=8.894, P=0.003）. There were no significant correlations between HER-2 gene rs2517954, and rs2517955 loci polymorphisms, and breast cancer patients＇ clinical stage, tumor size, histological grade, lymph node metastasis, ER, PR, Ki-67 and P53 expressions （P〉0.05）. Conclusion： HER-2 gene rs2517955 loci polymorphism is correlated with its protein expression. Further studies may be helpful to elucidate the mechanism of HER-2 protein expression in breast cancer.