CAJ | 학술논문

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。
목적：기왕연구발현TGF-β통로가능시영향결직장암예후적분자통로，유우인충유전차이성，중국인군중시부여질병상관상불학정。문중탐토안휘환남지구인군결직장암예후상관적유전인소。방법종향수방안휘성무호시중의의원급환남의학원부속의원2013년1월지2014년4월수치적결직장암환자52례，제취DNA보존병대선취적5개후선기인진행분형，평개환자기인다태성위점（ single nucleotide polymorphism， SNP）재불동유전모형하여결직장암예후적관련。결과전화생장인자β（ TGF-β）통로상POU2AF1기인SNP rs10749971적A등위기인재가성、은성유전모형하，균현저증가구유Ⅲ결직장암환자적복발풍험（HR＝1．968，P＝0．004；HR＝2．174，P＝0．010）；BMP2기인SNP rs961253적C등위기인재은형유전모형하，가동시증가Ⅲ기결직장암환자복발（HR＝1．992，P＝0．005）급사망풍험（HR＝3．161，P＝0．007），SMAD7기인SNP rs4464148적A등위기인재현성유전모형하가현저강저Ⅱ기급Ⅲ기결직장암환자적사망풍험（ HR＝0．382， P＝0．017； HR＝0．230，P＝0．006）。대우Ⅲ기결직장암환자예후적다기인루적효응현시，기인고풍험조가명현증가환자적사망풍험（ HR＝15．512，95％CI：1．611～149．360）。결론재불동유전모형하，TCF-β통로상적POU2AF1、BMP2급SMAD7기인적SNP위점돌변여결직장암환자예후존재관련，차수착휴대불리기인수증가，환자적사망풍험증가。
Objective Previous study found TGF-βpathway might be the molecular pathway influencing the prognosis of colo-rectal 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 colorectal 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-βsignaling 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 SNP rs4464148 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:1.611-149.360). Conclusion In different genetic models, SNP locus mutation within gene POU2AF1, BMP2 and SMAD7 on TGF-βpathway was associated with the prognosis of patients with colorectal cancer.With the increase of the number of unfavorable genes, the death risk increases accordingly.