dc.contributor.author | Lønning, Per Eystein | |
dc.contributor.author | Berge, Elisabet Ognedal | |
dc.contributor.author | Bjørnslett, Merete Pauline | |
dc.contributor.author | Minsaas, Laura | |
dc.contributor.author | Chrisanthar, Ranjan | |
dc.contributor.author | Vetti, Hildegunn Høberg | |
dc.contributor.author | Dulary, Cécile | |
dc.contributor.author | Busato, Florence | |
dc.contributor.author | Bjørneklett, Silje | |
dc.contributor.author | Eriksen, Christine | |
dc.contributor.author | Kopperud, Reidun Kristin | |
dc.contributor.author | Axcrona, Ulrika | |
dc.contributor.author | Davidson, Ben | |
dc.contributor.author | Bjørge, Line | |
dc.contributor.author | Evans, D. Gareth | |
dc.contributor.author | Howell, Anthony | |
dc.contributor.author | Salvesen, Helga | |
dc.contributor.author | Janszky, Imre | |
dc.contributor.author | Hveem, Kristian | |
dc.contributor.author | Romundstad, Pål Richard | |
dc.contributor.author | Vatten, Lars Johan | |
dc.contributor.author | Tost, Jörg | |
dc.contributor.author | Dørum, Anne | |
dc.contributor.author | Knappskog, Stian | |
dc.date.accessioned | 2019-03-12T11:52:08Z | |
dc.date.available | 2019-03-12T11:52:08Z | |
dc.date.created | 2018-05-27T12:29:19Z | |
dc.date.issued | 2018 | |
dc.identifier.citation | Annals of Internal Medicine. 2018, 168 (5), 326-334. | nb_NO |
dc.identifier.issn | 0003-4819 | |
dc.identifier.uri | http://hdl.handle.net/11250/2589683 | |
dc.description.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, 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. | nb_NO |
dc.language.iso | eng | nb_NO |
dc.publisher | American College of Physicians | nb_NO |
dc.title | White blood cell BRCA1 promoter methylation status and ovarian cancer risk | nb_NO |
dc.title.alternative | White blood cell BRCA1 promoter methylation status and ovarian cancer risk | nb_NO |
dc.type | Journal article | nb_NO |
dc.type | Peer reviewed | nb_NO |
dc.description.version | publishedVersion | nb_NO |
dc.source.pagenumber | 326-334 | nb_NO |
dc.source.volume | 168 | nb_NO |
dc.source.journal | Annals of Internal Medicine | nb_NO |
dc.source.issue | 5 | nb_NO |
dc.identifier.doi | 10.7326/M17-0101 | |
dc.identifier.cristin | 1586958 | |
dc.description.localcode | This article will not be available due to copyright restrictions (c) 2018 by American College of Physicians | nb_NO |
cristin.unitcode | 194,65,20,0 | |
cristin.unitname | Institutt for samfunnsmedisin og sykepleie | |
cristin.ispublished | true | |
cristin.fulltext | original | |
cristin.qualitycode | 2 | |