结直肠癌患者外周血赖氨酰氧化酶基因多态性及其临床意义

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目的探讨外周血赖氨酰氧化酶(LOX)基因rs2278226位点多态性与结直肠癌患者肿瘤转移的关系。方法选取2012年1月—2015年6月间在河北省人民医院住院治疗的164例转移结直肠癌患者(转移组)、218例无转移结直肠癌患者(无转移组),并选择同期进行体格检查的健康者340名(对照组),检测其血清肿瘤标志物癌胚抗原(CEA)、CA199、CA50和外周血LOX的水平。采用离心柱法提取各样本基因组DNA,PCR技术扩增目的基因后应用DNA直接测序技术检测3组患者外周血LOX基因rs2278226位点的多态性。采用Logistic回归分析LOX基因rs2278226多态位点与结直肠癌转移间的关系。结果转移组和无转移组的血清CEA、CA199、CA50和LOX水平均显著高于对照组(P值均<0.05)。转移组的血清CEA、CA199、CA50和LOX水平均显著高于无转移组(P值均<0.05)。PCR产物纯化后双向测序结果显示,LOX基因rs2278226位点存在两种单核苷酸多态性C和G,共有3种基因型:CC(突变纯合子)、CG(突变杂合子)、GG(非突变基因型)。转移组和无转移组的CG、CC基因型频率均显著高于对照组(P值均<0.05),转移组的CC基因型频率显著高于无转移组(P<0.05)。转移组和无转移组的C等位基因频率均显著高于对照组(P值均<0.05),转移组的C等位基因频率显著高于无转移组(P<0.05)。Logistic回归分析显示,CC基因型是结直肠癌转移的独立危险因素(OR=2.951,95%CI为1.198~4.687,P<0.05)。结论结直肠癌患者LOX基因rs2278226位点多态性与肿瘤转移有关。 Objective To investigate the relationship between rs2278226 polymorphism of peripheral blood lysyl oxidase (LOX) gene and tumor metastasis in patients with colorectal cancer. Methods A total of 164 patients with metastatic colorectal cancer (metastasis group) and 218 patients without metastatic colorectal cancer (without metastasis group) hospitalized in Hebei Provincial People’s Hospital from January 2012 to June 2015 were enrolled in this study. Physical examination of healthy 340 (control group), detection of serum tumor markers carcinoembryonic antigen (CEA), CA199, CA50 and peripheral blood LOX levels. The genomic DNA of each sample was extracted by centrifugal column method. After amplification of the target gene by PCR, the polymorphism of rs2278226 locus in LOX gene in peripheral blood was detected by DNA direct sequencing. Logistic regression analysis was used to analyze the relationship between rs2278226 polymorphism of LOX gene and metastasis of colorectal cancer. Results Serum levels of CEA, CA199, CA50 and LOX in patients with metastasis and without metastasis were significantly higher than those in control group (all P <0.05). The levels of serum CEA, CA199, CA50 and LOX in the metastatic group were significantly higher than those in the non-metastatic group (all P <0.05). The results of bi-directional sequencing showed that there are two SNPs C and G at rs2278226 in LOX gene. There are 3 genotypes in CCR gene: CC (mutant homozygote), CG (mutant heterozygote), GG ( Non-mutant genotype). The frequencies of CG and CC genotypes in metastatic group and non-metastatic group were significantly higher than those in control group (P <0.05). The frequency of CC genotype in metastatic group was significantly higher than that in non-metastatic group (P <0.05). The frequency of C allele was significantly higher in the metastasis group than in the control group (P <0.05). The frequency of C allele in the metastasis group was significantly higher than that in the non-metastasis group (P <0.05). Logistic regression analysis showed that CC genotype was an independent risk factor for colorectal cancer metastasis (OR = 2.951, 95% CI 1.198-4.687, P <0.05). Conclusion The rs2278226 polymorphism of LOX gene in patients with colorectal cancer is associated with tumor metastasis.
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