Clinicopathological significance of BRCA1 promoter hypermethylation in Thai breast cancer patients

Asian Pac J Cancer Prev. 2014;15(24):10585-9. doi: 10.7314/apjcp.2014.15.24.10585.

Abstract

Breast cancer susceptibility gene 1 (BRCA1), mapped on chromosome 17q21, is implicated in the mechanisms of cellular DNA repair. Inactivation of this gene is involved in the development of many human cancers, including breast cancer. This study aimed to investigate the prognostic value of BRCA1 promoter hypermethylation and expression in breast cancer cases. Sixty-one breast cancers were examined for BRCA1 hypermethylation by methylation-specific polymerase chain reaction (PCR), and 45 paired normal breast tissues were analyzed for altered BRCA1 mRNA levels by quantitative real-time reverse transcription-polymerase chain reaction (qRT- PCR). Aberrant methylation status in BRCA1 was detected in 15 of 61 cases (24.6%), while reduced expression was 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). Our findings indicated that BRCA1 promoter hypermethylation is a useful prognostic marker for breast cancer.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • BRCA1 Protein / genetics*
  • Breast / metabolism*
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology
  • Case-Control Studies
  • DNA Methylation*
  • Female
  • Follow-Up Studies
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Middle Aged
  • Neoplasm Grading
  • Neoplasm Staging
  • Prognosis
  • Promoter Regions, Genetic / genetics*
  • RNA, Messenger / genetics
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction
  • Thailand

Substances

  • BRCA1 Protein
  • BRCA1 protein, human
  • RNA, Messenger