Clinicopathological Significance of BRCA1 Promoter Hypermethylation in Thai Breast Cancer Patients

Abstract

Breast cancer susceptibility gene 1 (BRCA1), mapped on chromosome 17q21, is implicated in the mechanismsof cellular DNA repair. Inactivation of this gene is involved in the development of many human cancers, includingbreast cancer. This study aimed to investigate the prognostic value of BRCA1 promoter hypermethylation andexpression in breast cancer cases. Sixty-one breast cancers were examined for BRCA1 hypermethylation bymethylation-specific polymerase chain reaction (PCR), and 45 paired normal breast tissues were analyzed foraltered BRCA1 mRNA levels by quantitative real-time reverse transcription-polymerase chain reaction (qRTPCR).Aberrant methylation status in BRCA1 was detected in 15 of 61 cases (24.6%), while reduced expressionwas found in 7 of 45 (15.6%). BRCA1 hypermethylation was statistically associated with tumor grade III (p=0.04),a high frequency of stage IIB (p=0.02), and triple-negative phenotype (OR= 3.64, 95%CI =1.1-12.3, p=0.03). Ourfindings indicated that BRCA1 promoter hypermethylation is a useful prognostic marker for breast cancer.