TLR4基因启动子单核苷酸多态性与结直肠癌临床预后的关系

Correlation between Single Nucleotide Polymorphism of TLR4 Gene Promoter and Clinical Prognosis of Colorectal Cancer

目的：探讨Toll样受体（TLR）基因启动子单核苷酸多态性（SNP）与结直肠癌临床预后的关系。方法：收集我院2006年1月到2010年1月收治的结直肠癌患者200例,通过PCR扩增外周血DNA,经过查找数据库发现TLR4基因启动子区域有rs137853920、ss77136219多态位点,对所有患者随访5年,比较不同手术方式、美国癌症联合委员会（AJCC）分期、分化程度患者的总生存时间（OS）率和疾病无进展时间（PFT）率,分析基因型频率以及单倍体频率对患者生存影响。结果：200例患者生存时间在4～60个月,中位生存时间为54个月,OS率和PFT率在不同手术方式、癌症AJCC分期、分化程度患者间差异均具有统计学意义（P〈0.05）;对生存资料进行多因素的Cox回归分析,结果显示rs137853920基因多态位点基因型AA、AG、GG具有较好的预后（P〈0.05）,而ss77136219基因多态位点基因型GG、GA、AA具有较差预后（P〈0.05）。rs137853920、ss77136219多态位点共有四个单倍体型分别为AA、AG、GA、GG,频率分别为26.3%、21.7%、38.5%、21.6%,经过Cox多因素分析AG型患者具有较好预后（P〈0.05）,而GG型患者具有较差预后（P〉0.05）。结论：TLR4基因启动子SNP可以作为结直肠癌临床预后的特异指标。

Objective： To investigate the correlation between the single nucleotide polymorphism （SNP） of Toll-like receptors （TLR4） gene promoter and the clinical prognosis of colorectal cancer. Methods： A total of 200 cases of colorectal cancer, who were ad- mitted to First Affiliated Hospital of Jiamusi University from January 2006 to January 2010, were collected. The peripheral blood DNA was arnplifed by PCR method, there were rs137853920, ss77136219 polymorphic sites in the region of TLR4 gene promoter found in the database. All the patients have been followed up for 5 years. The overall survival （OS） rate and progression-free time （PFT） rate in the pa- tients with different operation modes, American joint committee on cancer （AJCC） stages and differentiation degrees were compared. The influence ofgenotype frequency and haploid frequency on the survival situation was analyzed. Results： The survival time of 200 pa- tients was during 4 to 60 months, and the median survival time was 54 months. OS rate and PFT rate in the patients with different opera- tion modes, AJCC stages and differentiation degrees had statistical difference（P〈0.05）. The results of Cox multivariate regression analysis on the survival data showed that the genotypes AA, AG, GG ofrs137853920 polymorphic site had better prognosis （P〈0.05）, while the genotypes GG, GA, AA ofss77136219 polymorphism site had poor prognosis（P〈0.05）. The four haplotypes ofrs137853920, ss77136219 polymorphic site were AA, AG, GA, GG, the frequencies were 26.3%, 21.7%, 38.5%, 21.6% respectively. The Cox multivariate regres- sion analysis showed that the patients with haplotype AG had better prognosis （P〈0.05）, while the patients with haplotype GG had poor prognosis （P〈0.05）. Conclusion： SNP of TLR4 gene promoter can be used as a specific index to understand the clinical prognosis of col-orectal cancer.