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White blood cell BRCA1 promoter methylation status and ovarian cancer risk

Lønning, Per Eystein; Berge, Elisabet Ognedal; Bjørnslett, Merete Pauline; Minsaas, Laura; Chrisanthar, Ranjan; Vetti, Hildegunn Høberg; Dulary, Cécile; Busato, Florence; Bjørneklett, Silje; Eriksen, Christine; Kopperud, Reidun Kristin; Axcrona, Ulrika; Davidson, Ben; Bjørge, Line; Evans, D. Gareth; Howell, Anthony; Salvesen, Helga; Janszky, Imre; Hveem, Kristian; Romundstad, Pål Richard; Vatten, Lars Johan; Tost, Jörg; Dørum, Anne; Knappskog, Stian
Journal article, Peer reviewed
Published version
Åpne
Lønning (Låst)
Permanent lenke
http://hdl.handle.net/11250/2589683
Utgivelsesdato
2018
Metadata
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  • Institutt for samfunnsmedisin og sykepleie [1706]
  • Publikasjoner fra CRIStin - NTNU [19694]
Originalversjon
Annals of Internal Medicine. 2018, 168 (5), 326-334.   10.7326/M17-0101
Sammendrag
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, BRCA1methylation 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.
Utgiver
American College of Physicians
Tidsskrift
Annals of Internal Medicine

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