Potential Use of DOK7 Gene Methylation Level in the Peripheral Blood Cells as a Biomarker in Early Diagnosis of Sporadic Breast Cancer

Breast cancer is the most important and prevalent cancer in women that can be managed if detected in the early stages. Recently, there has been much focus on the use of epigenetic changes such as DNA methylation in early detection of cancer. As recent research has put forth DOK7 CpG Island methylation as an epimarker, in the present study, using a quantification method, a cohort of Iranian sporadic breast cancer patients are studied compared to healthy women. In this matched case-control study (by ethnicity andage), blood samples were collected and the extracted DNA was controlled and after sonication, the MeDIP process started. The enrichment estimation is the MeDIP control step and after that, all of the H19-ICR, GAPDH-promoter and DOK7-CpG were standardized with appropriate efficiency for Real-Time PCR relative quantification process. Comparison of the Relative Quantification (RQ) of the enriched methylated DNA in the DOK7 gene CpG island in the two groups showed a significant difference (P=0.01). The mean RQ was 0.961 (0.91) in patients and 0.44 (0.46) in the control group. The ROC curve analysis showed AUC= 0.671 and the estimated cut-off for this gene RQ was 1.136; in this cut-off, the odd sratio (OR) was 4.773 (95% CI; 1.52-14.98). It should be noted that the methylation level for DOK7-CpG in DCIS was significantly higher than ICD patients (P-Value= 0.023). Based on our results, we conclude that increased levels of DNA methylation in the DOK7-CpG in peripheral leukocyte associate with breast cancer and after further studies, it can be used as an early diagnostic indicator or a biomarker for breast cancer susceptibility.