Dai Jianbo, Gao Haiyan, Xue Jiao, Lin Weijia, Zheng Lin
Department of Thyroid and Breast Surgery, The Affiliated Changzhou No.2 People's Hospital of Nanjing Medical University, Changzhou, China.
Genet Test Mol Biomarkers. 2019 Jun;23(6):393-400. doi: 10.1089/gtmb.2018.0309. Epub 2019 May 7.
The protein AXIN2 is involved in the negative feedback regulation of the Wnt/β-catenin signaling pathway; it functions by promoting β-catenin degradation. mutations have been studied in various cancers. In this study, we genotyped three single nucleotide polymorphisms in the gene and investigated their association with the risk of breast cancer (BC) in the Chinese Han population. In a population of 415 BC patients and 528 controls the expression of was measured using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and compared with the overall survival (OS) of BC patients analyzed through Oncomine and Kaplan-Meier plotter databases. Bioinformatic analyses demonstrated that mRNA levels were downregulated in BC patients; this in turn correlated with a poorer survival rate for BC patients. The polymorphisms rs11079571 and rs3923087, but not rs3923086, were associated with an increased risk of BC. The minor allele containing genotypes of polymorphism rs3923087 were positively associated with lymph node metastases. A haplotype analysis demonstrated that the ATA haplotype was correlated with an increased risk of BC. In conclusion, the downregulation of AXIN2 is related to poorer OS for BC patients. Its polymorphisms rs11079571 and rs3923087 confer susceptibility to BC. These findings should be confirmed with larger studies that include more diverse ethnic populations.
蛋白质AXIN2参与Wnt/β-连环蛋白信号通路的负反馈调节；它通过促进β-连环蛋白降解发挥作用。已在多种癌症中对其突变进行了研究。在本研究中，我们对该基因中的三个单核苷酸多态性进行了基因分型，并调查了它们与中国汉族人群乳腺癌（BC）风险的关联。在415例BC患者和528例对照人群中，使用基质辅助激光解吸/电离飞行时间质谱法测量AXIN2的表达，并与通过Oncomine和Kaplan-Meier绘图仪数据库分析的BC患者的总生存期（OS）进行比较。生物信息学分析表明，BC患者中AXIN2 mRNA水平下调；这反过来又与BC患者较差的生存率相关。多态性rs11079571和rs3923087（而非rs3923086）与BC风险增加相关。多态性rs3923087包含次要等位基因的基因型与淋巴结转移呈正相关。单倍型分析表明，ATA单倍型与BC风险增加相关。总之，AXIN2的下调与BC患者较差的OS相关。其多态性rs11079571和rs3923087赋予了对BC的易感性。这些发现应通过包括更多不同种族人群的更大规模研究来证实。
