B7-H1基因rs4143815位点多态性与结直肠癌发病风险的关联研究

目的：B7-H1是肿瘤免疫治疗的一个靶点，位于其3'-非翻译区的rs4143815位点C/G多态性可影响其与miR-570的结合，进而影响B7-H1的表达。本研究旨在探讨B7-H1基因rs4143815位点多态性与结直肠癌发病风险的相关性。方法：采集215例结直肠癌患者和236例年龄性别匹配的健康对照人群外周静脉血，并收集手术切除结直肠癌和癌旁正常组织样本65例，直接测序法检测B7-H1基因rs4143815多态性，运用卡方检验分析B7-H1基因rs4143815多态性与结直肠癌发病风险的相关性；定量PCR检测B7-H1 mRNA表达。结果：结直肠癌和对照组中均检测到B7-H1基因rs4143815多态性的3种基因型，即CC、CG和GG基因型。结直肠癌和癌旁正常组织中均检测到B7-H1 mRNA的表达。与CC基因型相比，GG和CG/GG基因型显著增加了结直肠癌的发病风险GG与CC相比：OR_调整=1.99，95% CI （1.19，3.34），P=0.008；CG/GG与CC相比：OR_调整=1.58，95% CI （1.06，2.36） P=0.02]。与C等位基因相比，G等位基因显著增加了结直肠癌的发病风险OR_调整=1.48，95% CI （1.14，1.93），P=0.004]。B7-H1 mRNA在结直肠癌组织中的表达明显高于癌旁组织（P=0.02），并且B7-H1基因rs4143815位点GG基因型携带者B7-H1 mRNA水平明显高于CC基因型携带者（P=0.03）。结论：B7-H1基因rs4143815位点GG基因型可能通过增加B7-H1 mRNA表达，进而增加了结直肠癌的发病风险。

Association between rs4143815 polymorphism in the B7-H1 gene and risk of colorectal cancer

OBJECTIVE: B7-H1 is a target of tumor immunotherapy. A polymorphism rs4143815C/G in the 3'-untranslated region of B7-H1 can affect its binding to miR-570,which in turn influences the expression of B7-H1. The aim of this study was to investigate the association between the rs4143815 polymorphism and risk of colorectal cancer (CRC). METHODS: Peripheral venous blood was collected from 215 patients with CRC and 236 age- and gender-matched healthy controls. Tumor tissues and adjacent normal tissues were collected from 65 patients with CRC. The rs4143815 polymorphism was genotyped by direct sequencing and B7-H1 mRNA levels were examined by quantitative PCR. The association between the rs4143815 polymorphism in the B7-H1 gene and the risk of CRC was analyzed using chi-square test. RESULTS: Three genotypes of the rs4143815 polymorphism in the B7-H1 gene were detected in both cases and controls,that is CC,CG and GG genotype. The B7-H1 mRNA expression was observed in CRC tissues and adjacent normal tissues. The rs4143815 GG and CG/GG genotypes were associated with a significantly increased risk of CRC compared with the CC genotypeGG vs. CC:adjusted OR=1.99,95%CI (1.19,3.34),P=0.008;CG/GG vs. CC:adjust OR=1.58,95%CI (1.06,2.36),P=0.02]. Similarly,the G allele was associated with a significantly increased risk of CRC compared with the C alleleadjusted OR=1.48,95%CI(1.14,1.93),P=0.004]. The expression of B7-H1 mRNA in CRC tissues was significantly higher than that in adjacent tissues (P=0.02). Moreover,the B7-H1 mRNA level in the rs4143815 GG genotype carriers was significantly higher than that in the rs4143815 CC genotype carriers (P=0.03). CONCLUSION: The rs4143815 GG genotype in the B7-H1 gene may increase the expression of B7-H1 mRNA and result in an increased risk of CRC.