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Genetic Epidemiology
Article . 2014 . Peer-reviewed
License: Wiley TDM
Data sources: Crossref
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Genome-Wide Investigation of Regional Blood-Based DNA Methylation Adjusted for Complete Blood Counts Implicates BNC2 in Ovarian Cancer

Ovarian cancer DNA methylation study implicates BNC2
Authors: Ellen L. Goode; Brooke L. Fridley; Melissa C. Larson; Mine S. Cicek; Stacey J. Winham; Sebastian M. Armasu; Kimberly R. Kalli; +1 Authors

Genome-Wide Investigation of Regional Blood-Based DNA Methylation Adjusted for Complete Blood Counts Implicates BNC2 in Ovarian Cancer

Abstract

Due to its potential as a biomarker for early cancer detection, blood-based DNA methylation (DNAm) is of interest in cancer research. Specifically, highly predictive mechanisms for early detection of epithelial ovarian cancer (EOC) are desired, so previous studies have compared DNAm between EOC cases and controls. However, case-control studies are confounded by the distribution of white blood cell types through an immune response induced by the cancer. Rather than determining the distribution of the cell types manually or investigating isolated cell types, an alternative approach involves the use of complete blood count (CBC), which is routinely collected. In the analysis of an EOC case-control study of DNAm, we incorporate CBC measures to adjust for this confounding and compare DNAm between 242 EOC cases and 181 age-matched controls (assayed on the Illumina Infinium HumanMethylation27 or HumanMethylation450 Beadchips), at both the individual CpG and CpG island levels. We found that adjustment for leukocyte distribution using CBC measurements dramatically reduced confounding, with 62 single CpG sites found to be associated with EOC status after adjustment (P < 5E-8). Additionally, regional DNAm was assessed by applying principal components analysis to CpG islands. The top associated CpG island (P = 7E-6) was located in the promoter/transcription start site of the human basonuclin 2 gene (BNC2), a known susceptibility gene for EOC risk identified through GWAS. Follow-up studies are necessary to establish the role of BNC2 in blood-based DNA and EOC, including prospective studies to validate this region as a potential biomarker and predictor of EOC susceptibility.

Keywords

Adult, Ovarian Neoplasms, Adolescent, Genome, Human, Neutrophils, DNA, Carcinoma, Ovarian Epithelial, DNA Methylation, Middle Aged, Blood Cell Count, Epigenesis, Genetic, DNA-Binding Proteins, Organ Specificity, Case-Control Studies, Humans, CpG Islands, Female, Neoplasms, Glandular and Epithelial, Promoter Regions, Genetic, Maternal Age

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citations
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
20
Top 10%
Average
Top 10%
bronze