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Normal tissue BRCA1 promoter methylation is positively associated with risk for high-grade serous ovarian cancer


The role of normal tissue gene promoter methylation in cancer risk is poorly understood.
A study has evaluated associations between normal tissue BRCA1 methylation and ovarian cancer risk.

Researchers conducted two case-control studies to investigate the effect of normal tissue BRCA1 methylation on ovarian cancer risk, including 934 patients and 1698 control participants in the initial study; 607 patients and 1984 control participants in the validation study.

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 ).

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.

In conclusion, constitutively normal tissue BRCA1 promoter methylation is positively associated with risk for high-grade serous ovarian cancer. ( Xagena )

Lønning PE et al, Ann Intern Med 2018;doi:10.7326/M17-0101.

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