title: Genetic polymorphism of miR-196a as a prognostic biomarker for early breast cancer.
abstract: BACKGROUND
  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.
  
  
  METHODS
  Three SNPs of miR-196a (rs3746444, rs11614913, and rs1044129) were selected using in silico analysis and genotyped using the Sequenom MassARRAY.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Oncology/Hematology, Kyungpook National University Medical Center, Kyungpook National University School of Medicine, Daegu, Republic of Korea.
authors.forename: Soo Jung
authors.initials: SJ
authors.lastname: Lee
authors.affiliation: Department of Oncology/Hematology, Kyungpook National University Medical Center, Kyungpook National University School of Medicine, Daegu, Republic of Korea.
authors.forename: Jong Won
authors.initials: JW
authors.lastname: Seo
authors.affiliation: Department of Oncology/Hematology, Kyungpook National University Medical Center, Kyungpook National University School of Medicine, Daegu, Republic of Korea yschae@knu.ac.kr jyparkmd@knu.ac.kr.
authors.forename: Yee Soo
authors.initials: YS
authors.lastname: Chae
authors.affiliation: Department of Oncology/Hematology, Kyungpook National University Medical Center, Kyungpook National University School of Medicine, Daegu, Republic of Korea.
authors.forename: Jong Gwang
authors.initials: JG
authors.lastname: Kim
authors.affiliation: Department of Oncology/Hematology, Kyungpook National University Medical Center, Kyungpook National University School of Medicine, Daegu, Republic of Korea.
authors.forename: Byung Woog
authors.initials: BW
authors.lastname: Kang
authors.affiliation: Department of Surgery, Kyungpook National University Medical Center, Kyungpook National University School of Medicine, Daegu, Republic of Korea.
authors.forename: Wan Wook
authors.initials: WW
authors.lastname: Kim
authors.affiliation: Department of Surgery, Kyungpook National University Medical Center, Kyungpook National University School of Medicine, Daegu, Republic of Korea.
authors.forename: Jin Hyang
authors.initials: JH
authors.lastname: Jung
authors.affiliation: Department of Surgery, Kyungpook National University Medical Center, Kyungpook National University School of Medicine, Daegu, Republic of Korea.
authors.forename: Ho Yong
authors.initials: HY
authors.lastname: Park
authors.affiliation: Department of Pathology, Kyungpook National University Medical Center, Kyungpook National University School of Medicine, Daegu, Republic of Korea.
authors.forename: Ji Yun
authors.initials: JY
authors.lastname: Jeong
authors.affiliation: Department of Pathology, Kyungpook National University Medical Center, Kyungpook National University School of Medicine, Daegu, Republic of Korea yschae@knu.ac.kr jyparkmd@knu.ac.kr.
authors.forename: Ji-Young
authors.initials: JY
authors.lastname: Park
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D060787:Neoplasm Grading; D009364:Neoplasm Recurrence, Local / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D009367:Neoplasm Staging; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D015996:Survival Rate; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; C542543:MIRN196 microRNA, human; D035683:MicroRNAs
keywords: MicroRNA; breast cancer; miR-196a; prognosis; rs11614913