| dc.description.abstract | Breast cancer is the most common type of cancer in women worldwide. Screening programs have been established in many countries to prevent deaths from breast cancer by detecting the disease at an early stage and arranging a suitable treatment strategy. However, one of the weaknesses of the screening programs is the risk of overdiagnosis followed by overtreatment. Thus, there is an interest of additional methods or biomarkers that can help us diagnose breast cancer earlier and more precise with less invasive methods. In the last years, there has been an increasing interest of using miRNAs as early detection biomarkers of cancer because of their regulatory functions and aberrant expression in cancer. However, less is known about the miRNA dynamics in circulation prior to cancer diagnosis. Our study identified miRNA signals in 383 pre-diagnostic serum samples donated up to 10 years prior to diagnosis, compared to 195 frequency matched cancer-free controls from the Janus Serum Bank Cohort. The results of the differential analyses showed that seven miRNAs were consistently, significantly, and highly deregulated in pre-diagnostic serum samples from women with breast cancer. These were miR-574-5p, miR-10393-3p, miR-4676-5p, miR-1307-5p, miR-1183, miR-9-5p and miR-1-3p. Investigation of miR-574-5p showed that its large effect size may be due to batch effects. Thus, the biological relevance of this miRNA should be investigated in future breast cancer studies. Furthermore, our results revealed that the differentially abundant miRNAs were time to diagnosis specific and were highly deregulated 0-3.1 years prior to diagnosis. These results may be linked to the different hallmarks of cancer and/or undiagnosed advanced breast cancer. Our results encourage further investigation of the differentially abundant miRNAs identified in this study. | eng |