White Blood Cell BRCA1 Promoter Methylation Status and Ovarian Cancer Risk.
Ann Intern Med
; 168(5): 326-334, 2018 03 06.
Article
en En
| MEDLINE
| ID: mdl-29335712
ABSTRACT
Background:
The role of normal tissue gene promoter methylation in cancer risk is poorly understood.Objective:
To assess associations between normal tissue BRCA1 methylation and ovarian cancer risk.Design:
2 case-control (initial and validation) studies.Setting:
2 hospitals in Norway (patients) and a population-based study (control participants).Participants:
934 patients and 1698 control participants in the initial study; 607 patients and 1984 control participants in the validation study. Measurements All patients had their blood sampled before chemotherapy. White blood cell (WBC) BRCA1 promoter methylation was determined by using methylation-specific quantitative polymerase chain reaction, and the percentage of methylation-positive samples was compared between population control participants and patients with ovarian cancer, including the subgroup with high-grade serous ovarian cancer (HGSOC).Results:
In the initial study, BRCA1 methylation was more frequent in patients with ovarian cancer than control participants (6.4% vs. 4.2%; age-adjusted odds ratio [OR], 1.83 [95% CI, 1.27 to 2.63]). Elevated methylation, however, was restricted to patients with HGSOC (9.6%; OR, 2.91 [CI, 1.85 to 4.56]), in contrast to 5.1% and 4.0% of patients with nonserous and low-grade serous ovarian cancer (LGSOC), respectively. These findings were replicated in the validation study (methylation-positive status in 9.1% of patients with HGSOC vs. 4.3% of control participants-OR, 2.22 [CI 1.40 to 3.52]-4.1% of patients with nonserous ovarian cancer, and 2.7% of those with LGSOC). The results were not influenced by tumor burden, storage time, or WBC subfractions. In separate analyses of young women and newborns, BRCA1 methylation was detected in 4.1% (CI, 1.8% to 6.4%) and 7.0% (CI, 5.0% to 9.1%), respectively.Limitations:
Patients with ovarian cancer were recruited at the time of diagnosis in a hospital setting.Conclusion:
Constitutively normal tissue BRCA1 promoter methylation is positively associated with risk for HGSOC. Primary Funding Source Norwegian Cancer Society.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Neoplasias Ováricas
/
Regiones Promotoras Genéticas
/
Metilación de ADN
/
Leucocitos
Tipo de estudio:
Etiology_studies
/
Observational_studies
/
Risk_factors_studies
Límite:
Adolescent
/
Adult
/
Aged
/
Aged80
/
Female
/
Humans
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Middle aged
/
Newborn
País/Región como asunto:
Europa
Idioma:
En
Revista:
Ann Intern Med
Año:
2018
Tipo del documento:
Article