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miR-146a 基因变异可改变中国人群结直肠癌易感性。

A genetic variant in miR-146a modifies colorectal cancer susceptibility in a Chinese population.

机构信息

Department of Genetic Toxicology, The Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, China.

出版信息

Arch Toxicol. 2013 May;87(5):825-33. doi: 10.1007/s00204-012-1004-2. Epub 2013 Jan 10.

DOI:10.1007/s00204-012-1004-2
PMID:23306950
Abstract

MicroRNAs (miRNAs) are a family of endogenous, small, noncoding RNA molecules that involved in a wide range of biological processes including differentiation, proliferation, and apoptosis. A polymorphism G>C (rs2910164) is located in the stem region opposite to the mature miR-146a sequence. In our study, we investigated whether rs2910164 is associated with the risk of colorectal cancer (CRC) in a Chinese population. We genotyped the rs2910164 polymorphism using TaqMan method and evaluated the association with CRC risk in a case-control study, including 1,147 CRC patients and 1,203 cancer-free controls. Logistic regression models were used to assess the genetic effects on the development of CRC. Overall, we found that rs2910164 was significantly associated with the reduced CRC risk [GC/CC versus GG: adjusted odds ratio (OR) = 0.78, 95 % confidence intervals (CIs) = 0.66-0.93]. In the stratification analysis, this decreased risk was also pronounced among non-smokers (0.75, 0.61-0.93), non-drinkers (0.77, 0.63-0.94), and no family history of cancer (0.79, 0.65-0.95). Furthermore, GC/CC genotypes were associated with reduced CRC susceptibility in intermediate differentiated CRC (0.75, 0.62-0.90), and similar effect was observed in patients with the advanced stage tumor (Dukes C and D) (0.76, 0.61-0.93). In conclusion, our results suggest that miR-146a rs2910164 may contribute to the susceptibility to CRC in a Chinese population. Further larger population-based prospective and functional studies are needed to validate our findings.

摘要

微小 RNA(miRNAs)是一组内源性、小、非编码的 RNA 分子,参与广泛的生物学过程,包括分化、增殖和凋亡。一个位于成熟 miR-146a 序列对面的茎区的 G>C(rs2910164)多态性。在我们的研究中,我们调查了 rs2910164 是否与中国人群结直肠癌(CRC)的风险相关。我们使用 TaqMan 方法对 rs2910164 多态性进行基因分型,并在病例对照研究中评估了其与 CRC 风险的关联,包括 1147 例 CRC 患者和 1203 例无癌对照。使用逻辑回归模型评估遗传效应对 CRC 发展的影响。总的来说,我们发现 rs2910164 与 CRC 风险降低显著相关[GC/CC 与 GG:调整后的比值比(OR)=0.78,95%置信区间(CI)=0.66-0.93]。在分层分析中,这种降低的风险在非吸烟者(0.75,0.61-0.93)、不饮酒者(0.77,0.63-0.94)和无癌症家族史者(0.79,0.65-0.95)中也很明显。此外,GC/CC 基因型与中等分化 CRC 的 CRC 易感性降低相关(0.75,0.62-0.90),在晚期肿瘤(Dukes C 和 D)患者中也观察到类似的效果(0.76,0.61-0.93)。总之,我们的结果表明,miR-146a rs2910164 可能在中国人群中导致 CRC 的易感性。需要进一步进行更大的基于人群的前瞻性和功能研究来验证我们的发现。

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