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Genome-wide investigation of regional blood-based DNA methylation adjusted for complete blood counts implicates BNC2 in ovarian cancer.
- Source :
-
Genetic epidemiology [Genet Epidemiol] 2014 Jul; Vol. 38 (5), pp. 457-66. Date of Electronic Publication: 2014 May 22. - Publication Year :
- 2014
-
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.<br /> (© 2014 WILEY PERIODICALS, INC.)
- Subjects :
- Adolescent
Adult
Blood Cell Count
Carcinoma, Ovarian Epithelial
Case-Control Studies
DNA genetics
DNA metabolism
Epigenesis, Genetic
Female
Humans
Maternal Age
Middle Aged
Neutrophils cytology
Organ Specificity
Promoter Regions, Genetic genetics
Transcription Initiation Site
Young Adult
CpG Islands genetics
DNA Methylation genetics
DNA-Binding Proteins genetics
Genome, Human genetics
Neoplasms, Glandular and Epithelial genetics
Ovarian Neoplasms genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1098-2272
- Volume :
- 38
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Genetic epidemiology
- Publication Type :
- Academic Journal
- Accession number :
- 24853948
- Full Text :
- https://doi.org/10.1002/gepi.21815