BRCA1 Promoter Methylation and Clinicopathological Characteristics in Sporadic Breast Cancer Patients in Indonesia

Document Type: Research Articles

Authors

1 Division of Surgical Oncology Medical School of Andalas University, M.Djamil Hospital, Padang, Indonesia.

2 Andalas Cancer and Stem Cells Research Center, Universitas Andalas, Padang, Indonesia.

3 Doctoral Program, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada, Yogyakarta City, Indonesia.

Abstract

Objective: The aim of this study was to investigate the BRCA1 promoter methylation and clinicopathological
characteristics in sporadic breast cancer patients in Indonesia. Methods: In this cohort study, we selected 90 patients
with stage I-III who had definitive surgery at our institution in 2011-2014. Demographic and clinical data regarding
pathological stage, breast cancer treatment, outcome etc. were collected from the medical records. Twelve patients had
incomplete information on follow up and 18 samples had insufficient tissues for the experiment. Sixty patients with
adequate cancer tissues and complete follow up record were analyzed, only 56 patients were analyzed because 4 samples
mRNA expression could not be detected. The Mann–Whitney U tests for non-normally distributed groups were used
to compare the levels expression of BRCA1 mRNA between methylated and non-methylated samples. Chi-square tests
were used to compare methylation status, BRCA1 mRNA expression and clinicopathological characteristics. P value
< 0.05 was considered as statistically significant correlation. Data analysis was held by using the GraphPad PRISM 7
(GraphPad Software Inc., USA). Results: DNA and RNA were isolated from primary tumor tissues of 56 breast cancer
patients. BRCA1 promoter methylation was detected in 48 of 56 patients (85%). Level of BRCA1 mRNA expression was
associated with decreased methylation level in the BRCA1 promoter regions suggesting the role of epigenetic silencing.
However, there was no statistically significant association among methylation levels, BRCA1 mRNA transcript level
with clinicopathological factors. Conclusion: To our knowledge, this is the first study investigating methylation status
and level of BRCA1 mRNA transcripts among breast cancer patients in Indonesia. We found that the prevalence of
BRCA1 promoter methylation is higher than other studies from different populations. However, further investigation
involving larger number of patients is required.

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