Abstract
BackgroundIn recent years, hypermethylation of gene promoters has emerged as one of the fundamental mechanisms for the inactivation of tumor suppressor genes and has a potential role in the early detection of breast cancer. The present study is a case-control study aimed to quantify the methylation levels in the promoters of secretoglobin 3A1 (SCGB3A1), and ataxia-telangiectasia mutated (ATM) genes and evaluate their relation to clinicopathological features of the tumor in a cohort of Egyptian female patients with breast cancer.MethodsGenomic deoxyribonucleic acid (DNA) was extracted from 100 tissue samples, 50 breast cancer tissues and 50 adjacent non-cancerous breast tissues, then, it was subjected to bisulfite conversion. The converted DNA was amplified by real-time PCR; then, pyrosequencing was performed to quantify DNA methylation levels in four CpG sites in ATM and SCGB3A1 gene promoters. The methylation data were presented as the percentage of average methylation of all the observed CpG sites and were calculated for each sample and each gene.ResultsThe percentage of DNA methylation of the SCGB3A1 promoter was significantly higher in the tumor group than in the normal group (P= 0.001). However, a non-statistical significance difference was found in the DNA methylation percentage of the ATM promoter in the tumor group compared to the normal group (P = 0.315). The SCGB3A1 promoter methylation frequency was significantly associated with estrogen receptors (ER) and progesterone receptors (PR) positive tumors, lymph node metastasis, and lymphovascular invasion. However, no association was found between ATM methylation status and the different clinicopathological features of the tumor.ConclusionsThe findings of this work showed that the SCGB3A1 promoter methylation was significantly higher in the tumor group and was significantly associated with different clinicopathologic features in breast cancer. It may be considered as a suitable biomarker for diagnosis and prognosis. However, the promoter methylation levels of the ATM gene in breast cancer cases were unable to distinguish between breast cancer tissues and adjacent normal tissues, and there is no evidence that epigenetic silencing by ATM methylation has a role in breast cancer pathogenesis.
Highlights
In recent years, hypermethylation of gene promoters has emerged as one of the fundamental mechanisms for the inactivation of tumor suppressor genes and has a potential role in the early detection of breast cancer
The current findings demonstrated that deoxyribonucleic acid (DNA) methylation levels of the secretoglobin 3A1 (SCGB3A1) promoter were significantly higher in the tumor group compared to the normal group (P = 0.001)
In conclusion, SCGB3A1 promoter methylation was significantly higher in the tumor group and was significantly associated with different clinicopathologic features of the tumor
Summary
Hypermethylation of gene promoters has emerged as one of the fundamental mechanisms for the inactivation of tumor suppressor genes and has a potential role in the early detection of breast cancer. The mechanisms of epigenetic alterations include DNA methylation, alterations in chromatin condensation, histone modifications, and RNA interference [1]. Despite early detection and improvement in its management, its mortality increases annually, accounting for 14% of the total cancer deaths [4]. It is considered a complex multifactorial disease. There is increasing evidence that hypermethylation of tumor-related genes may have added to the pathogenesis of breast cancer in recent years [6]
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