A genetic variant in miR-146a modifies colorectal cancer susceptibility in a Chinese population
A genetic variant in miR-146a modifies colorectal cancer susceptibility in a Chinese population
复制标题
DOI：
10.1007/s00204-012-1004-2
复制
发表时间：
2013-05-01
影响因子：
6.1
通讯作者：
Wang, Meilin
中科院分区：
文献类型：
--
作者：
Ma, Lan;Zhu, Lingjun;Wang, Meilin
MicroRNA (miRNA) 是一类内源性小非编码 RNA 分子，参与分化、增殖和凋亡等多种生物过程。多态性 G > C (rs2910164) 位于与成熟 miR-146a 序列相对的茎区。在我们的研究中，我们调查了 rs2910164 是否与中国人群中结直肠癌 (CRC) 的风险相关。我们使用 TaqMan 方法对 rs2910164 多态性进行基因分型，并在一项病例对照研究中评估了与 CRC 风险的关联，该研究包括 1,147 名 CRC 患者和 1,203 名无癌症对照者。使用逻辑回归模型评估遗传对结直肠癌发展的影响。总体而言，我们发现 rs2910164 与 CRC 风险降低显着相关 [GC/CC 与 GG：调整优势比 (OR) = 0.78，95% 置信区间 (CI) = 0.66-0.93]。在分层分析中，这种风险降低在不吸烟者（0.75，0.61-0.93）、不饮酒者（0.77，0.63-0.94）和无癌症家族史（0.79，0.65-0.95）中也很明显。此外，GC/CC 基因型与中间分化 CRC 的 CRC 易感性降低相关（0.75、0.62-0.90），并且在晚期肿瘤患者（Dukes C 和 D）中观察到类似的效果（0.76、0.61-0.93）。总之，我们的结果表明 miR-146a rs2910164 可能导致中国人群对 CRC 的易感性。需要进一步更大规模的基于人群的前瞻性和功能研究来验证我们的研究结果。
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.