结直肠癌患者β-纤维蛋白原基因多态性和血浆纤维蛋白原水平相关性的研究

摘要

背景与目的：结直肠癌患者病程中常伴有血浆纤维蛋白原(fibrinogen，Fg)浓度的升高。该研究探讨结直肠癌人群中FGBβ基因-448G/A、-148C/T、-1420G/A、-854G/A的单核苷酸多态性(single nucleotide polymorphism，SNP)频率分布和血浆Fg浓度的关系，分析其对肿瘤发生、发展的影响。方法：采集194例结直肠癌患者和74例健康者外周血，用实时荧光定量多聚酶链反应(real-time fluorescence quantitative PCR， RTFQ-PCR)法分析FGBβ基因频率分布，用Clauss凝固法检测血浆Fg浓度。结果：结直肠癌转移组和无转移组的血浆Fg浓度均较对照组显著升高(P<0.05)。疾病组中FGBβ-148T等位基因频率和突变型基因频率均显著高于对照组(P<0.05)。各组人群中FGBβ-148T携带者的血浆Fg浓度均明显高于非携带者(P<0.05)。在Ⅳ期患者中FGBβ-148C/T突变型者中位PFS较野生型者差异无统计学意义(P>0.05)。结论：结直肠癌患者体内Fg浓度升高，提示其可能参与恶性肿瘤发生、发展的过程。FGBβ-148C/T位点的SNP是导致血浆Fg浓度改变的原因之一，但与Ⅳ期患者的预后无关。%Background and purpose:Patients with colorectal cancer are often accompanied by the increase of plasma ifbrinogen concentration. This study aimed to investigate the distribution characteristics of beta-ifbrinogen gene-448G/A, -148C/T, -1420G/A and -854G/A polymorphism and plasma ifbrinogen (Fg) concentration in patients with colorectal cancer. Furthermore, we analyzed their effects on the occurrence and development of cancer.Methods:The level of plasma Fg was quantiifed by using Clauss clotting method.FGBβ gene polymorphisms were identiifed by re-al-time lfuorescence quantitative PCR (RTFQ-PCR) in 194 colorectal cancer patients and 74 healthy controls.Results:The plasma Fg levels in tumor metastasis group and non-metastasis group were signiifcantly higher than that in control group, respectively (P<0.05). Compared with control group, the frequencies of -148T allele and mutation genotype were notably higher in disease group (P<0.05). In all the groups, the plasma Fg levels of those with -148T allele were higher than those without -148T allele (P<0.05). In stageⅣ patients, there was no difference in PFS between -148T wild gen-otype group and mutation genotype group (P>0.05).Conclusion:Plasma Fg concentration in patients with colorectal cancer was signiifcantly raised, which suggests that Fg may play a role in the occurrence and development of colorectal cancer. The beta-ifbrinogen gene -148C/T polymorphism is one of the reasons that cause plasma Fg elevation, but has no correlation with prognosis of patients with stageⅣ colorectal cancer.