Abstract
Breast cancer, a leading cause of death among women in most countries worldwide, is rapidly increasing in incidence in Vietnam. One of biomarkers is the disruption of the genetic material including epigenetic changes like DNA methylation. With the aim of finding hypermethylation at CpG islands of promoter of BRCA1 gene, belonged to the tumor suppressor gene family, as the biomarker for breast cancer in Vietnamese population, sensitive methyl specific PCR (MSP) was carried out on 115 samples including 95 breast cancer specimens and 20 normal breast tissues with other diseases which were obtained from Ho Chi Minh City Medical Hospital, Vietnam. The result indicated that the frequency of BRCA1 hypermethylation reached 82.1% in the cases (p<0.001). In addition, the DNA hypermethylation of this candidate gene increased the possibility to be breast cancer with high incidence via calculated odd ratios (p<0.05). In conclusion, hypermethylation of this candidate gene could be used as the promising biomarker application with Vietnamese breast cancer patients.
Highlights
With the aim of finding hypermethylation at CpG islands of promoter of BRCA1 gene, belonged to the tumor suppressor gene family, as the biomarker for breast cancer in Vietnamese population, sensitive methyl specific PCR (MSP) was carried out on 115 samples including 95 breast cancer specimens and 20 normal breast tissues with other diseases which were obtained from Ho Chi Minh City Medical Hospital, Vietnam
In Vietnam, breast cancer is the most frequent malignancy leading to the death for female, constituting in certain has increased from a crude rate of 13.8 per 100,000 women in 2000 to 28.1 per 100,000 women in 2010 (Nguyen at al., 2013)
In patient with breast cancer, gene amplification of HER2 which is a member of the epidermal growth factor receptor family, is found to be present in 15-30% newly diagnosed breast cancer cases and the mutations in the tumor suppressor gene p53 is presented in 18%25% of primary breast carcinomas (Alsner at al., 2000; Kotoe at el., 2009)
Summary
In Vietnam, breast cancer is the most frequent malignancy leading to the death for female, constituting in certain has increased from a crude rate of 13.8 per 100,000 women in 2000 to 28.1 per 100,000 women in 2010 (Nguyen at al., 2013). The objective of present study was to determine the hypermethylation occurred in breast cancer gene (BRCA1 gene), one of tumor suppressor genes, applied in Vietnamese population. The DNA methylation usually occurs in the CpG islands located in or near the promoter of over 70% of all gene (Tanett et al, 2011; Fatemeh et al, 2012; Wei-Jia et al, 2012). It is found that hypermethylation in promoter CpG islands of BRCA1 leads to the loss of expression of BRCA1, especially, in breast cancer (Xu et al, 2009). We determined quantitatively the hypermethylation at CpG islands of promoter belongs to BRCA1, in both Vietnamese breast cancer patients of all stages from premalignant to advanced metastatic breast. Phuong Kim Truong et al tumor and healthy specimens by the MSP (Methylation specific PCR) method
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