miR-146a单核苷酸基因rs2910164多态性与结肠癌发生及转移的关系
Correlation between polymorphism of single nucleotide gene rs2910164 in miR-146a and incidence and metastasis of colorectal cancer

目的 研究miR-146a C→G（rs2910164）单核苷酸多态性（SNP）及miR-146a表达水平与结肠癌的关系。方法 结肠癌患者106例（CRC组），取结肠癌及自身正常结肠组织；另取正常结肠黏膜53例作为对照（Con组）。使用基因测序方法确定SNP的等位基因，分析不同基因型与结肠癌发生及转移的关系。转移患者定义为T1组，无转移患者定义为T0组。使用real-time PCR法检测并比较不同基因型结肠组织中miR-146a表达量；比较癌组织与其自身正常结肠组织中miR-146a表达量；同时比较T1组与T0组癌组织miR-146a表达量。结果 CRC组与Con组miR-146a基因型分布不同，Logistic回归显示GG及GC是结肠癌发病的危险因素；在Con组结肠组织中GG及GC基因型携带者miR-146a表达量较CC基因型携带者低；结肠癌患者中癌组织miR-146a水平较其自身癌旁正常组织低。T1组及T0组基因型分布亦有所不同，T1组GG基因型比例较高，Logistic回归显示GG是结肠癌转移的危险因素之一；T1组患者癌组织中miR-146a表达量进一步降低。携带GG基因型者血管内皮生长因子（EGFR）及白介素-1受体相关激酶（IRAK-1）表达水平较高。结论 miR-146a多态性中的G等位基因是结肠癌发病和转移的危险因素之一，可能与该多态现象导致的较低的miR-146a表达量，继而产生相对高表达的EGFR和IRAK-1有关。
： Objective To investigate the correlation between colorectal cancer (CRC) and the single nucleotide polymorphism (SNP) in miR-146a C→G (rs2910164), as well as the expression level of miR-146a. Methods Colorectal cancer and adjacent normal tissues in 106 CRC patients (the CRC group) and normal tissues in 53 healthy controls (the control group) were obtained. Alleles of SNP were determined with gene sequencing method and the correlation between different genotypes and the occurrence and metastasis of CRC was analyzed. Patients with or without metastasis were assigned to the T1 group or the T0 group. Real-time-PCR was used to measure and compare miR-146a expressions in colon tissues with different genotypes. miR-146a expressions in cancer and adjacent normal tissues were compared and miR-146a expressions in cancer tissues were compared between the T1 group and the T0 group. Results The distribution of miR-146a genotypes in the CRC group was different from that in the control group. The Logistic regression analysis showed that GG and GC genotypes were risk factors for CRC. The controls carrying GG and GC genotypes had lower miR-146a expressions in colon tissues as compared with those carrying CC genotype. Cancer tissues in CRC patients had lower miR-146a expressions as compared with adjacent normal tissues. The distribution of genotypes in the T1 group was also different from that in the T0 group. The T1 group had a higher proportion of GG genotype. The Logistic regression analysis showed that GG genotype was a risk factor for CRC metastasis. Patients in the T1 group had lower miR-146a expressions in cancer tissues. GG genotype carriers had higher expression levels of EGFR and IRAK-1. Conclusion The G allele in the SNP of miR-146a is a risk factor for the incidence and metastasis of CRC. The mechanism may be related to lower miR-146a expression caused by the SNP and resulting higher expressions of EGFR and IRAK-1