影响安徽省皖南地区结直肠癌患者预后的TGF-β通路候选基因关联研究  

Candidate gene association study of TGF-βpathway in progonosis of patients with colorectal cancer in Wanan area

作　　者：沈丽娟 钟芳芳 吴平平 曹晓智[3] 卢林明[4] 

机构地区：[1]芜湖市中医医院病理科基因诊断室,芜湖241000 [2]芜湖市第二人民医院病理科,芜湖241000 [3]皖南医学院附属第二医院病理科,芜湖241000 [4]皖南医学院附属弋矶山医院病理科,芜湖241000

出　　处：《医学研究生学报》2015年第9期957-961,共5页Journal of Medical Postgraduates

摘　　要：目的 既往研究发现TGF-β通路可能是影响结直肠癌预后的分子通路,由于人种遗传差异性,中国人群中是否与疾病相关尚不确定。文中探讨安徽皖南地区人群结直肠癌预后相关的遗传因素。方法 纵向随访安徽省芜湖市中医医院及皖南医学院附属医院2013年1月至2014年4月收治的结直肠癌患者52例,提取DNA保存并对选取的5个候选基因进行分型,评价患者基因多态性位点（single nucleotide polymorphism,SNP）在不同遗传模型下与结直肠癌预后的关联。结果转化生长因子β（TGF-β）通路上POU2AF1基因SNP rs10749971的A等位基因在加性、隐性遗传模型下,均显著增加具有Ⅲ结直肠癌患者的复发风险（HR=1.968,P=0.004;HR=2.174,P=0.010）;BMP2基因SNP rs961253的C等位基因在隐形遗传模型下,可同时增加Ⅲ期结直肠癌患者复发（HR=1.992,P=0.005）及死亡风险（HR=3.161,P=0.007）,SMAD7基因SNP rs4464148的A等位基因在显性遗传模型下可显著降低Ⅱ期及Ⅲ期结直肠癌患者的死亡风险（HR=0.382,P=0.017;HR=0.230,P=0.006）。对于Ⅲ期结直肠癌患者预后的多基因累积效应显示,基因高风险组可明显增加患者的死亡风险（HR=15.512,95%CI：1.611-149.360）。结论 在不同遗传模型下,TCF-β通路上的POU2AF1、BMP2及SMAD7基因的SNP位点突变与结直肠癌患者预后存在关联,且随着携带不利基因数增加,患者的死亡风险增加。Objective Previous study found TGF-βpathway might be the molecular pathway influencing the prognosis of coinrectal cancer, while it was uncertain whether Chinese population is associated with the disease. The article was to evaluate the genetic factors associated with prognosis in colorectal cancer. Methods 52 cases patients with coloreetal cancer were followed-up for 36 months in our hospitals from January 2013 to August 2014 . Their DNAs were extracted and stored and gene typing were carried out in 5 candidate genes to detect the association between SNPs and the prognosis in colorectal cancer. Results The results showed that within the TGF-β signaling pathway, after adjusting for Bonferroni multiple testing, allele A of SNP rs10749971 located in gene POU2AF1 was associated with the recurrence of patients with stage Ⅲ disease under additive and recessive genetic models （ HR = 1. 968, P=0.004; HR=2. 174, P=0. 010）. Allele C of SNP rs961253 in the gene BMP2 could increase the recurrence risk （ HR = 1. 992, P = 0. 005 ） and the death risk （ HR = 3. 161, P = 0. 007） of patients with stage Ⅲ disease under recessive genetic models. Allele A of SNPrs4464148 in SMAD7 gene could significantly decrease the death risk of patients with stage Ⅱ and Ⅲ colorectal cancer under dominant genetic model （ HR = 0. 382, P = 0. 017 ; HR = 0. 230, P = 0. 006）. In addition, accumulated effects of several adverse genes showed gene high risk group could increase the risk of death for patients with stage III colorectal cancer significantly （HR = 15. 512, P = 0. 036; 95% CI：I. 611 -149. 360）. Conclusion In different genetic models, SNP locus mutation within gene POU2AF1, BMP2 and SMAD7 on TGF-β pathway was associated with the prognosis of patients with colorectal cancer. With the increase of the number of unfavorable genes, the death risk increases accordingly.

关 键 词：结直肠癌 预后 基因多态性 TGF-β通路 

分 类 号：R735.3[医药卫生—肿瘤]