Genetic polymorphism of miR-196a as a prognostic biomarker for early breast cancer

As microRNAs (miRNA) may play important roles in tumorigenesis by regulating the expression of proto-oncogenes or tumor suppressor genes, the present study analyzed single nucleotide polymorphisms (SNPs) located in miRNA and miRNA-binding sites of various genes and their impact on prognosis for 452 patients with early breast cancer. Three SNPs of miR-196a (rs3746444, rs11614913, and rs1044129) were selected using in silico analysis and genotyped using the Sequenom MassARRAY. The median age of patients was 48 years, and 283 (62.6%) were estrogen and/or progesterone receptor (ER/PgR)-positive, 86 (19.0 %) had human epidermal growth factor receptor 2 (HER2)-overexpressing, and 77 (17.0%) had triple-negative early breast cancer. During the median follow-up of 6.9 years, 67 (14.8%) relapses and 55 (12.2%) deaths were recorded. Among the three polymorphisms, the C allele of miR-196a rs11614913T>C was significantly associated with worse disease-free (DFS) and distant DFS (DDFS) when adjusted for clinical and pathological parameters. In particular, the prognostic impact of rs11614913 was limited to the hormone receptor-expressing subtype, where the patients bearing the CC genotype showed worse survival in terms of DFS and DDFS compared with the patients with the TT or TC genotype as a recessive model (hazard ratio=2.610, p=0.003 for DFS; hazard ratio=2.730, p=0.013 for DDFS). The current study provides evidence that the miR-196a rs11614913T>C polymorphisms are possible prognostic biomarker for patients with hormone receptor-expressing early breast cancer.