A genetic variant in the promoter region of miR-34b/c is associated with a reduced risk of colorectal cancer
A genetic variant in the promoter region of miR-34b/c is associated with a reduced risk of colorectal cancer
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DOI：
10.1515/hsz-2012-0297
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发表时间：
2013-03-01
影响因子：
3.7
通讯作者：
Zhang, Lin
中科院分区：
文献类型：
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作者：
Gao, Lin-Bo;Li, Li-Juan;Zhang, Lin
miR-34家族成员被描述为潜在的肿瘤抑制因子，在结直肠癌（CRC）中下调。miR-34的缺失会损害tp53介导的细胞死亡，而miR-34的过表达则会诱导细胞凋亡。预测pri-miR-34b/ C启动子区域的潜在功能多态性（即rs4938723T/C）会影响GATA-X结合位点。我们旨在研究miR-34b/c rs4938723和TP53 Arg72Pro多态性与CRC风险之间的关系。我们利用聚合酶链反应-限制性片段长度多态性和DNA测序技术对347例结直肠癌患者和488名健康对照者的这两种多态性进行了基因分型。我们发现，与TT基因型和T等位基因相比，miR-34b/ C rs4938723的CC基因型和C等位基因与CRC风险显著降低相关（CC vs. TT：校正OR=0.56; 95% CI, 0.34-0.91; C vs. T：校正OR=0.78; 95% CI, 0.64-0.97）。在联合分析中，携带rs4938723 CT/CC和TP53 GG基因型的受试者也观察到临界意义（校正OR=0.66; 95% CI, 0.43-0.99）。这些发现表明，pri-miR-34b/c启动子区域的rs4938723是CRC发展的保护因子。由于显著性是边际的，需要进一步的重复性研究来证实这些结果。
The miR-34 family members, described as potential tumor suppressors, were downregulated in colorectal cancer (CRC). Loss of miR-34 impairs TP53-mediated cell death, while overexpression of miR-34 induces apoptosis. A potentially functional polymorphism (i.e., rs4938723T/C) in the promoter region of pri-miR-34b/c was predicted to influence the GATA-X binding sites. We aimed to investigate the association between miR-34b/c rs4938723 and TP53 Arg72Pro polymorphisms and the risk of CRC. We genotyped the two polymorphisms in 347 CRC patients and 488 healthy controls using polymerase chain reaction-restriction fragment length polymorphism and DNA sequencing assay. We found that the CC genotype and C allele of the miR-34b/c rs4938723 were associated with a significantly decreased risk of CRC compared with the TT genotype and T allele (CC vs. TT: adjusted OR=0.56; 95% CI, 0.34-0.91; C vs. T: adjusted OR=0.78; 95% CI, 0.64-0.97). In combined analysis, a borderline significance was also observed in subjects carrying the rs4938723 CT/CC and TP53 GG genotypes (adjusted OR=0.66; 95% CI, 0.43-0.99). These findings indicate that the rs4938723 in the promoter region of pri-miR-34b/c was a protective factor for the development of CRC. As the significance is marginal, further replication studies are warranted to confirm these results.