Breast cancer (BC) is one of the most common causes of death among women in the world. This study investigated the role of global DNA methylation (5mC) and hypoxia-inducible factor 1 alpha (HIF-1α) levels in BC disease progression. Blood samples were collected from 40 patients with benign breast tumors, 40 patients with malignant breast tumors, and 40 healthy subjects. Patients with malignant breast tumors were divided into two groups: women in stage II (low-level), and patients in stages III and IV (high-level). Genomic DNA was isolated from whole blood samples from the subjects and used for global DNA methylation. Furthermore, the levels of HIF-1α expression were measured. The results showed that the levels of 5mC in patients with BC and benign breast tumors were considerably lower (0.538 ± 0.03 and 0.432 ± 0.04%, respectively), compared to the control (0.619 ± 0.05%). Furthermore, there was a significant (p ≤ 0.05) decrease in levels of 5mC in BC patients at stages III and IV compared to control. However, there were no significant differences between low-level and high-level stages. The HIF-1α levels of patients in both the benign breast tumors and BC were insignificant (923.35 ± 72.42 and 1386.03 ± 102.01pg/ml, respectively), compared to the control (825.5 ± 62.36 pg/ml). Although, BC patients at low levels showed no significant difference in HIF-1α levels compared with patients at high levels. The findings indicated that variations in 5mC levels across different stages and types of breast tumors may serve as a prognostic indicator for the development of BC and also implicated HIF-1α in the development of BC.
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