INTERNATIONAL CONGRESS OF
CancerGenetics
Investigation of Common Genetic Variants Involved in Breast Cancer and the Interacting Roles of MicroRNAs and Obesity in Disease Pathogenesis
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Farzaneh Ramezani Hombari ,1,*
1. Shahid Beheshti University of Medical Sciences, Health Park, Hakimieh, Second West Floor (Genomics Laboratory)
- Introduction: Obesity, particularly in postmenopausal women, is a well-established independent risk factor for breast cancer. Underlying mechanisms include increased circulating oestrogen, chronic inflammation, insulin resistance and epigenetic alterations.MicroRNAs (miRNAs), which are key post-transcriptional regulators of gene expression, have emerged as critical mediators that link obesity-related metabolic dysregulation to the development of breast cancer. This study aimed to investigate the impact of weight loss on circulating microRNA (miRNA) profiles and their regulatory roles in obesity-associated breast cancer pathways.
- Methods: In a 12-month randomised controlled trial (RCT), overweight/obese postmenopausal women were assigned to one of three groups: a calorie-restricted diet; moderate-to-vigorous exercise; or a combination of both. Changes in 23 previously identified circulating miRNAs implicated in obesity, breast cancer, and related biological processes were assessed. Bioinformatic analysis integrated data from the TCGA, miRTarBase, KEGG and GWAS databases to identify gene targets and signalling pathways regulated by these miRNAs.
- Results: Participants who lost more than 10% of their baseline weight exhibited significant alterations in key circulating miRNAs, including miR-21, miR-155, miR-221/222 and miR-34a. These miRNAs modulate genes involved in the PI3K/AKT/mTOR, JAK/STAT and oestrogen receptor signalling pathways, thereby affecting tumour suppressors (e.g. BRCA1 and PTEN) and oncogenes (e.g. HER2 and MYC). We observed a dose-response relationship between the extent of weight loss and the magnitude of changes in miRNA expression.
- Conclusion: Circulating miRNAs act as potential molecular links between obesity and breast cancer, and may serve as non-invasive biomarkers for the early detection and stratification of risk. Furthermore, the therapeutic modulation of cancer-associated miRNAs (e.g. using antagomiRs or mimics) shows promise as a targeted intervention for obese women at high risk of breast cancer.These findings highlight the usefulness of integrative multi-omics and bioinformatics in clarifying the relationship between obesity and cancer, and in guiding personalised treatment strategies.
- Keywords: Micro RNA, Obesity, breast cancer, Variants
