结直肠癌的Wnt信号通路相关基因突变的研究

Mutation of Wnt signaling pathway related genes in colorectal cancer

目的 探究AXIN1、AXIN2基因多态性与结直肠癌遗传易感性的相关性。 方法 以临床确诊结直肠癌患者288例作为病例样本,健康对照者320例作为健康对照,使用激光解吸电离飞行时间质谱(MALDI-TOFMS)技术进行单核苷酸多态性(SNP)分型。SNP选择按照标签SNPs(tagSNPs)方法进行挑选,单体型的构建则应用SHESIS软件。 结果 等位基因模型下,AXIN1基因rs1805105等位基因增加结直肠癌的风险,OR值=1.53(1.351~1.732),P值<0.001。其他相关SNP位点等位基因未发现相关性。逻辑回归分析显示AXIN1基因rs1805105TT基因型相比,CT基因型与CC基因型与结直肠癌相关,P值均<0.001。CT基因型联合CC基因型与TT基因型相比,结直肠癌的易感性风险比为3.212(2.466~4.184),P值<0.001。单倍型分析显示AXIN1基因C-C-A单倍型与结直肠癌发病风险相关,OR=1.124(1.084~1.453),P值<0.001。 结论 AXIN1基因rs1805105基因多态性可能与结直肠癌的易感性相关。

Objective To explore the relationship between polymorphisms of AXIN1 and AXIN2 genes and genetic susceptibility to colorectal cancer. Methods Single nucleotide polymorphism (SNP) was typed by laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) in 288 patients with clinically confirmed colorectal cancer and 320 healthy controls. SNP wasselected according to tag SNPs method, and SHESIS software wasused to construct haplotypes. Results In the allele model, the rs1805105 allele of AXIN1 gene increased the risk of colorectal cancer (OR=1.53(1.351~1.732), P<0.001). No correlation was found among other SNP alleles. Logistic regression analysis showed that compared with rs1805105 TT genotype of AXIN1 gene, CT genotype and CC genotype were correlated with colorectal cancer, and P value was <0.001. Compared with TT genotype, OR of CT genotype combined with CC genotype to colorectal cancer was 3.212 (2.466-4.184), P value <0.001. Haplotype analysis showed that C-C-A haplotype of AXIN1 gene was associated with the risk of colorectal cancer (OR=1.124 (1.084-1.453), P<0.001). Conclusion The rs1805105 polymorphism of AXIN1 gene may be associated with the susceptibility to colorectal cancer.