title: Downregulation of microRNAs 145-3p and 145-5p is a long-term predictor of postmenopausal breast cancer risk: The ORDET prospective study.
abstract: BACKGROUND
  miRNAs have been implicated in the regulation of key metabolic, inflammatory, and malignant pathways; hence, they might be considered both predictors and players of cancer development.
  
  
  METHODS
  Using a case-control study design nested in the ORDET prospective cohort study, we addressed the possibility that specific mRNAs can serve as early predictors of breast cancer incidence in postmenopausal women. We compared leukocyte miRNA profiles of 133 incident postmenopausal breast cancer cases and profiles of 133 women who remained healthy over a follow-up period of 20 years.
  
  
  RESULTS
  The analysis identified 20 differentially expressed miRNAs, 15 of which were downregulated. Of the 20 miRNAs, miR145-5p and miR145-3p, each derived from another arm of the respective pre-miRNA, were consistently and significantly downregulated in all the databases that we surveyed. For example, analysis of more than 1,500 patients (the UK Metabric cohort) indicated that high abundance of miR145-3p and miR145-5p was associated with longer, and for miR145-3p also statistically significant, survival. The experimental data attributed different roles to the identified miRNAs: Although the 5p isoform was associated with invasion and metastasis, the other isoform seems related to cell proliferation.
  
  
  CONCLUSIONS
  These observations and the prospective design of our study lend support to the hypothesis that downregulation of specific miRNAs constitutes an early event in cancer development. This finding might be used for breast cancer prevention.
  
  
  CONCLUSIONS
  The identification of the miRNAs as long-term biomarkers of breast cancer may have an impact on breast cancer prevention and early detection.
authors: Department of Oncology, Faculty of Health Science, McMaster University, Hamilton, Ontario, Canada. muti@mcmaster.ca.
authors: Paola
authors: P
authors: Muti
authors: Translational Oncogenomics Unit, Regina Elena Italian National Cancer Institute, Rome, Italy.
authors: Andrea
authors: A
authors: Sacconi
authors: The Statistics for Integrative Genomics and Methods Advancement Laboratory, Population Genomics Program, Department of Clinical Epidemiology and Biostatistics, Faculty of Health Sciences, McMaster University, Hamilton, Ontario, Canada.
authors: Ahmed
authors: A
authors: Hossain
authors: Translational Oncogenomics Unit, Regina Elena Italian National Cancer Institute, Rome, Italy.
authors: Sara
authors: S
authors: Donzelli
authors: Department of Physics of Complex Systems, Weizmann Institute of Science, Rehovot, Israel.
authors: Noa Bossel
authors: NB
authors: Ben Moshe
authors: Translational Oncogenomics Unit, Regina Elena Italian National Cancer Institute, Rome, Italy.
authors: Federica
authors: F
authors: Ganci
authors: Department of Preventive and Predictive Medicine, Fondazione Istituto Nazionale Tumori, Milano, Italy.
authors: Sabina
authors: S
authors: Sieri
authors: Department of Preventive and Predictive Medicine, Fondazione Istituto Nazionale Tumori, Milano, Italy.
authors: Vittorio
authors: V
authors: Krogh
authors: Department of Preventive and Predictive Medicine, Fondazione Istituto Nazionale Tumori, Milano, Italy.
authors: Franco
authors: F
authors: Berrino
authors: Translational Oncogenomics Unit, Regina Elena Italian National Cancer Institute, Rome, Italy.
authors: Francesca
authors: F
authors: Biagioni
authors: Department of Oncology, Faculty of Health Science, McMaster University, Hamilton, Ontario, Canada. Molecular Chemoprevention Group, Molecular Medicine Area, Regina Elena Italian National Cancer Institute, Rome, Italy.
authors: Sabrina
authors: S
authors: Strano
authors: The Statistics for Integrative Genomics and Methods Advancement Laboratory, Population Genomics Program, Department of Clinical Epidemiology and Biostatistics, Faculty of Health Sciences, McMaster University, Hamilton, Ontario, Canada.
authors: Joseph
authors: J
authors: Beyene
authors: Department of Biological Regulation, Weizmann Institute of Science, Rehovot, Israel.
authors: Yosef
authors: Y
authors: Yarden
authors: Department of Oncology, Faculty of Health Science, McMaster University, Hamilton, Ontario, Canada. Translational Oncogenomics Unit, Regina Elena Italian National Cancer Institute, Rome, Italy.
authors: Giovanni
authors: G
authors: Blandino
mesh_terms: D001943:Breast Neoplasms / Q000209:etiology* / Q000235:genetics; D016022:Case-Control Studies; D015536:Down-Regulation; D005260:Female; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D017698:Postmenopause; D011446:Prospective Studies; D014162:Transfection
chemical_list: D035683:MicroRNAs