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miR-143/145 启动子区域多态性与结直肠癌风险的关联。

Association between polymorphisms in the promoter region of miR-143/145 and risk of colorectal cancer.

机构信息

Department of Forensic Biology, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu, Sichuan 610041, PR China.

出版信息

Hum Immunol. 2013 Aug;74(8):993-7. doi: 10.1016/j.humimm.2013.04.019. Epub 2013 Apr 27.

DOI:10.1016/j.humimm.2013.04.019
PMID:23628392
Abstract

Emerging evidence suggests that down-regulated miRNAs play an important role in the carcinogenesis of colorectal cancer (CRC). Single nucleotide polymorphisms (SNPs) in the promoter region of miRNAs may disturb miRNAs processing, alter their expression, and ultimately affect an individual's susceptibility to CRC. We conducted a case-control study and analyzed twelve SNPs in the promoter region of miR-143/145 of 525 subjects including 242 cases with CRC and 283 controls using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. The mutant genotypes or alleles of rs41291957, rs353292, rs353293, and rs4705341 were significantly associated with an increased risk of CRC compared with the wild genotypes or alleles, while rs4705343, rs17796757, rs3733845, and rs3733846 were significantly associated with a decreased risk of CRC. When stratification analysis was done by different variables, such as tumor size, tumor site, differentiated status, clinical stage, and metastasis status, we found that patients with the mutant allele of rs41291957 had an increased risk to develop a tumor size larger than 5 cm. These findings suggest that SNPs in the promoter region of miR-143/145 may be related to the etiology of CRC. However, further larger studies with different ethnic origins are needed to confirm our results due to limited sample sizes in the study.

摘要

新出现的证据表明,下调的 microRNA 在结直肠癌(CRC)的癌变过程中发挥重要作用。microRNA 启动子区域的单核苷酸多态性(SNP)可能会干扰 microRNA 的加工,改变其表达,并最终影响个体对 CRC 的易感性。我们进行了一项病例对照研究,分析了 525 名受试者 miR-143/145 启动子区域的 12 个 SNP,包括 242 名 CRC 病例和 283 名对照,使用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)检测。与野生基因型或等位基因相比,rs41291957、rs353292、rs353293 和 rs4705341 的突变基因型或等位基因与 CRC 的风险增加显著相关,而 rs4705343、rs17796757、rs3733845 和 rs3733846 与 CRC 的风险降低显著相关。当按不同变量(如肿瘤大小、肿瘤部位、分化状态、临床分期和转移状态)进行分层分析时,我们发现 rs41291957 突变等位基因的患者发生肿瘤大小大于 5cm 的风险增加。这些发现表明,miR-143/145 启动子区域的 SNP 可能与 CRC 的病因学有关。然而,由于研究中样本量有限,需要进一步进行来自不同种族的更大规模研究来证实我们的结果。

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