A genetic variant in microRNA-146a is associated with sporadic breast cancer in a Southern Brazilian Population

Abstract MicroRNAs (miRNAs) play an essential role in gene expression and affect the development of tumours, including breast cancer (BC). Polymorphisms in miRNA genes can affect the interaction of miRNAs with their target messenger RNA by interfering, creating or disrupting target sites. The single nucleotide polymorphism (SNP) rs2910164, located in the seed region of miR146a, was shown to be associated with BC among different populations. In the present study, we investigated whether rs2910164 is associated with BC in 326 patients and 411 controls from a Brazilian population of predominantly European ancestry. The presence of the allele rs2910164*C was associated with an increased risk of BC (OR=1.4, 95% CI=1.03-1.85, p = 0.03). We also analysed publicly available RNA-seq data to evaluate if miR146a is differentially expressed in different subtypes of BC. Genotyping was performed by polymerase chain reaction with sequence-specific primers (PCR-SSP). By leveraging public data from TCGA database, we analysed 461 patients and found that miR146a is significantly more expressed in BC than in non-tumor tissue (1.47 fold, p = 0.02) and is expressed to a greater degree in aggressive BC subtypes.

摘要：微小RNA（microRNAs，miRNAs）在基因表达调控中发挥关键作用，并可影响包括乳腺癌（breast cancer, BC）在内的多种肿瘤的发生发展。miRNA基因的多态性可通过干扰、创建或破坏靶位点，影响miRNA与其靶信使RNA（messenger RNA, mRNA）的结合互作。位于miR146a种子区的单核苷酸多态性（single nucleotide polymorphism, SNP）rs2910164，已被证实与不同人群中的乳腺癌风险相关。本研究针对以欧洲血统为主的巴西人群中的326名乳腺癌患者与411名健康对照，探讨了rs2910164多态性与乳腺癌的关联。研究结果显示，携带rs2910164*C等位基因可显著升高乳腺癌发病风险（比值比OR=1.4，95%置信区间CI=1.03~1.85，p=0.03）。此外，本研究还分析了公开可用的RNA测序（RNA-seq）数据，以探究miR146a在不同乳腺癌亚型中的差异表达情况。基因分型采用序列特异性引物聚合酶链反应（polymerase chain reaction with sequence-specific primers, PCR-SSP）技术完成。借助癌症基因组图谱（The Cancer Genome Atlas, TCGA）数据库的公开数据，本研究对461名患者的样本进行分析后发现，miR146a在乳腺癌组织中的表达量显著高于非肿瘤组织（表达量较非肿瘤组织升高1.47倍，p=0.02），且在侵袭性乳腺癌亚型中表达水平更高。