Qi P, Wang L, Zhou B, Yao W J, Xu S, Zhou Y, Xie Z B
Department of Head-Neck and Breast Surgery, Xinxiang Central Hospital, Xinxiang, China
Department of General Surgery, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang, China.
Genet Mol Res. 2015 Jun 11;14(2):6289-96. doi: 10.4238/2015.June.11.2.
Single-nucleotide polymorphisms in microRNAs (miRNAs) may dramatically affect gene expression and subsequently alter individual susceptibility to cancer, and thus has become a research hotspot for many cancer types, including breast cancer. We recruited 321 breast cancer patients and 290 controls in our study. Four established miRNA single-nucleotide polymorphisms (mir-499 rs3746444 A>G; miR-27a rs895819 A>G; miR-196a2 rs11614913 T>C; miR-146a rs2910164 G/C) were detected using Taqman assays. Mature miRNA expression, allele distribution, and the association with clinical features were further analyzed. Our results showed that the miR146a rs2910164 G/C polymorphism was associated with an elevated risk of breast cancer (odds ratio = 1.85, 95% confidence interval = 1.03-3.32; P < 0.05). Compared with the ancestral T allele in miR-196a2 rs11614913, the variant C allele was consistently associated with an increased risk of breast cancer (odds ratio = 2.20, 95% confidence interval = 1.19-4.09, P < 0.01) and clinical pathological type (P < 0.01). miR-27a rs895819 A>G and miR-499 rs3746444 A>G were not associated with breast cancer risk. Analysis of mature miRNA expression confirmed that the variant C allele in miR146a rs2910164 and miR-196a2 rs11614913 dramatically inhibited production of their mature products. Our results suggested that miR-146a rs2910164 G>C and miR-196a2 rs11614913 T>C may be biomarkers for predicting breast cancer risk in the Chinese population.
微小RNA(miRNA)中的单核苷酸多态性可能会显著影响基因表达,进而改变个体患癌易感性,因此已成为包括乳腺癌在内的多种癌症类型的研究热点。我们在研究中招募了321例乳腺癌患者和290例对照。使用Taqman分析检测了4个已确定的miRNA单核苷酸多态性(mir-499 rs3746444 A>G;miR-27a rs895819 A>G;miR-196a2 rs11614913 T>C;miR-146a rs2910164 G/C)。进一步分析了成熟miRNA表达、等位基因分布及其与临床特征的关联。我们的结果表明,miR146a rs2910164 G/C多态性与乳腺癌风险升高相关(比值比=1.85,95%置信区间=1.03-3.32;P<0.05)。与miR-196a2 rs11614913中的祖先T等位基因相比,变异C等位基因始终与乳腺癌风险增加(比值比=2.20,95%置信区间=1.19-4.09,P<0.01)和临床病理类型相关(P<0.01)。miR-27a rs895819 A>G和miR-499 rs3746444 A>G与乳腺癌风险无关。成熟miRNA表达分析证实,miR146a rs2910164和miR-196a2 rs11614913中的变异C等位基因显著抑制其成熟产物的产生。我们的结果表明,miR-146a rs2910164 G>C和miR-196a2 rs11614913 T>C可能是预测中国人群乳腺癌风险的生物标志物。