CpG island tumor suppressor promoter methylation in non-BRCA-associated early mammary carcinogenesis.
Cancer Epidemiol Biomarkers Prev
; 18(3): 901-14, 2009 Mar.
Article
em En
| MEDLINE
| ID: mdl-19258476
ABSTRACT
BACKGROUND:
Only 5% of all breast cancers are the result of BRCA1/2 mutations. Methylation silencing of tumor suppressor genes is well described in sporadic breast cancer; however, its role in familial breast cancer is not known.METHODS:
CpG island promoter methylation was tested in the initial random periareolar fine-needle aspiration sample from 109 asymptomatic women at high risk for breast cancer. Promoter methylation targets included RARB (M3 and M4), ESR1, INK4a/ARF, BRCA1, PRA, PRB, RASSF1A, HIN-1, and CRBP1.RESULTS:
Although the overall frequency of CpG island promoter methylation events increased with age (P<0.0001), no specific methylation event was associated with age. In contrast, CpG island methylation of RARB M4 (P=0.051), INK4a/ARF (P=0.042), HIN-1 (P=0.044), and PRA (P=0.032), as well as the overall frequency of methylation events (P=0.004), was associated with abnormal Masood cytology. The association between promoter methylation and familial breast cancer was tested in 40 unaffected premenopausal women in our cohort who underwent BRCA1/2 mutation testing. Women with BRCA1/2 mutations had a low frequency of CpG island promoter methylation (15 of 15 women hadCONCLUSIONS:
This is the first evidence of CpG island methylation of tumor suppressor gene promoters in non-BRCA1/2 familial breast cancer.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Mama
/
Ilhas de CpG
Tipo de estudo:
Etiology_studies
/
Risk_factors_studies
Limite:
Female
/
Humans
Idioma:
En
Ano de publicação:
2009
Tipo de documento:
Article