【摘要】 目的：探讨沉默信息调节因子1（silent information regulator 1, SIRT1）基因单核苷酸多态性（single nucleotide polymorphisms, SNPs）与汉族乳腺癌发病风险的关联。方法：纳入105例汉族乳腺癌患者及90例汉族健康对照者，采用Sequenom MassARRAY检测SIRT1基因rs3740051、rs3758391、rs12778366和rs2394443位点的基因型。利用卡方检验分析哈代-温伯格平衡（Hardy-Weinberg equilibrium, HWE），采用多因素logistic回归分析检测SNPs与乳腺癌易感性及rs3758391位点的基因型与汉族乳腺癌临床病理特征的相关性。运用SHEsis软件对所选SNP位点进行连锁不平衡分析和单倍型分析。Western blot检测rs3758391位点基因型SIRT1蛋白表达。另纳入150例汉族乳腺癌及150例汉族健康者作为对照组，采用免疫组化检测SIRT1蛋白表达；logistic回归分析SIRT1高低表达与乳腺癌临床特征的关系；Kaplan-Meier网站分析SIRT1表达与患者预后的关联。结果：4个SNP位点均符合HWE检验（P>0.05）。SIRT1 rs3758391位点的TC/TC+CC基因型相较于TT基因型显著降低乳腺癌风险(TT vs TC:OR_adj=0.348,95%CI:0.157～0.773, P_adj=0.010; TT vs TC+CC:OR_adj=0.381, 95%CI:0.179～0.811, P_adj=0.012)，且与早期病程（I/II期）、较小肿瘤体积和较高的SIRT1蛋白表达水平相关（P<0.05）。乳腺癌组织中，SIRT1表达显著降低，低表达的SIRT1与较大肿瘤体积、淋巴结转移和无复发生存期较短相关（P<0.05）。结论：SIRT1rs3758391位点的TC/TC+CC基因型可能是汉族乳腺癌的保护性因素，可能通过调节SIRT1表达来降低乳腺癌风险并延缓病程。此外，SIRT1表达水平与乳腺癌临床特征及预后相关。更多还原

【Abstract】 AIM: To investigate the association between single nucleotide polymorphisms（SNPs） in the silent information regulator 1（SIRT1） gene and breast cancer risk in the Han Chinese population. METHODS: A total of 105 Han Chinese patients with breast cancer and 90 healthy controls were enrolled. Sequenom MassARRAY was used to detect the genotypes of SIRT1 gene loci, rs3740051, rs3758391, rs12778366 and rs2394443. The Hardy-Weinberg equilibrium（HWE） was analysed using the chi-square test. Multivariate logistic regression was employed to analyze the correlation between each SNP and breast cancer susceptibility, as well as the relationship between the rs3758391 genotype and the clinicopathological characteristics of breast cancer in Han Chinese women. SHEsis software was used to assess linkage disequilibrium and haplotypes of the selected SNPs. The impact of genotypes at rs3758391 locus on SIRT1 protein expression was examined using Western blot. An additional 150 Han Chinese women with breast cancer and 150 healthy controls were enrolled, and SIRT1 protein expression was assessed using immunohistochemistry. Logistic regression was performed to assess the relationship between high and low SIRT1 expression and the clinical characteristics of breast cancer. Kaplan-Meier website was used to determine the association between SIRT1 expression and patient prognosis. RESULTS: All four SNP loci conformed to the HWE test（P>0. 05）. The TC/TC+CC genotype of the SIRT1 rs3758391 locus significantly reduced the risk of breast cancer compared with the TT genotype(TT vs TC: OR_adj=0. 348, 95% CI: 0. 157～0. 773, P_adj=0. 010; TT vs TC+CC: OR_adj=0. 381, 95% CI: 0. 179～0. 811, P_adj=0. 012), and correlated with earlier disease course（stage I/II）, smaller tumor volume, and higher SIRT1 protein expression levels（P<0. 05）. SIRT1 expression was significantly lower in breast cancer tissues, and low SIRT1 expression was associated with larger tumor size, lymph node metastasis, and reduced recurrence-free survival（P<0. 05）. CONCLUSION: The TC/TC+CC genotype of the SIRT1 rs3758391 locus may be a protective factor for breast cancer in Han Chinese women, potentially reducing the risk of breast cancer and delaying disease progression by regulating SIRT1 expression. In addition, SIRT1 expression level is closely related to the clinical characteristics and prognosis of breast cancer.更多还原