title: 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 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.
authors.affiliation: Research Division, National Cancer Institute, Bangkok, Thailand E-mail : saelee@health.moph.go.th.
authors.forename: Pensri
authors.initials: P
authors.lastname: Saelee
authors.forename: Arkom
authors.initials: A
authors.lastname: Chaiwerawattana
authors.forename: Kumiko
authors.initials: K
authors.lastname: Ogawa
authors.forename: Young-Man
authors.initials: YM
authors.lastname: Cho
authors.forename: Danai
authors.initials: D
authors.lastname: Tiwawech
authors.forename: Vimol
authors.initials: V
authors.lastname: Suktangman
mesh_terms: D019313:BRCA1 Protein / Q000235:genetics*; D001940:Breast / Q000378:metabolism*; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D016022:Case-Control Studies; D019175:DNA Methylation; D005260:Female; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D011379:Prognosis; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013785:Thailand
chemical_list: D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D012333:RNA, Messenger