Abstract 2876: Genetic polymorphism in the mir-196a as a prognostic biomarker for early breast cancer

Abstract

Abstract Background: MicroRNAs (miRNA) may play important roles in tumorigenesis by regulating the expressions of proto-oncogenes or tumor suppressor genes. Single nucleotide polymorphisms (SNP) in miRNA-coding genes and miRNA binding site genes might affect miRNA-mediated gene regulation, thereby contributing to the susceptibility or prognosis of cancer. Accordingly, the present study analyzed SNPs located in miRNA and miRNA-binding sites of various genes and their impact on the prognosis for patients with early breast cancer (EBC) by altering miRNA binding efficiency. Methods: Four hundred and fifty-two consecutive patients with curative resection were enrolled in the present study. Three SNPs (rs11614913, rs3746444 and rs1044129 of miR-196a, miR-499a and miR-367, respectively) were selected in Silico analysis for the current study based on several miRNA database and HapMap database. The SNP genotyping was performed using the Sequenom MassARRAY. Results: The median age of all patients was 48 years, and 298 (66.7%) had ER/PR-positive EBC, 64 (14.3%) had HER2-overexpressed EBC, and 79 (17.7%) had triple-negative EBC. The pathologic stages after the surgical resection were as follows: stage I (n=174, 38.5%), stage IIA (n=168, 37.2%), stage IIB (n=54, 11.9%), and stage IIIA (n=56, 12.4%). During the median follow-up of 6.9 (range 0.37 -19.93) years, 67 (14.8%) relapses and 47 (10.4%) deaths occurred. Among the 3 polymorphisms miR-196a rs11614913T>C was significantly associated with disease-free survival (DFS) and distant DFS (DDFS) when adjusted for age, histologic grade, receptor status, and pathologic stage. In particular, the prognostic impact of rs11614913 was limited to the HR- expressed subtype, where the patients bearing the CC genotype showed worse survival in terms of DFS and DDFS compared with those with the TT or TC genotype as a recessive model (HR= 2.571 and P-value=0.031, HR= 4.263 and P-value=0.001, respectively). Meanwhile, there were no statistical differences in patient and tumor characteristics among each genotype of rs11614913. Conclusions: The current study provides evidence that the miR-196a rs11614913T>C polymorphism is a possible prognostic biomarker for patients with HR-expressed early breast cancer. Citation Format: Soo Jung Lee, Yee Soo Chae, Byung Woog Kang, Jong Gwang Kim, Ji-Young Park, Jin Hyang Jung, Ho Yong Park. Genetic polymorphism in the mir-196a as a prognostic biomarker for early breast cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2876. doi:10.1158/1538-7445.AM2014-2876