White Blood Cell BRCA1 Promoter Methylation Status and Ovarian Cancer Risk


    loading  Checking for direct PDF access through Ovid

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.

    loading  Loading Related Articles