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Epigenomics. 2016 Jan;8(1):55-66. doi: 10.2217/epi.15.97. Epub 2015 Dec 18.

Global measures of peripheral blood-derived DNA methylation as a risk factor in the development of mature B-cell neoplasms.

Author information

1
Cancer Epidemiology Centre, Cancer Council Victoria, Australia.
2
Concord General & Repatriation Hospital, NSW, Australia.
3
Centre for Epidemiology & Biostatistics, The University of Melbourne, Victoria, Australia.
4
Department of Pathology, The University of Melbourne, Victoria, Australia.
5
Centre for Big Data Research in Health, University of New South Wales, Australia.
6
VLSCI Life Sciences Computation Centre, The University of Melbourne, Victoria, Australia.
7
Human Genetics Foundation, Torino, Italy.
8
Department of Haematology, Peter MacCallum Cancer Centre, Victoria, Australia.
9
Sir Peter MacCallum Department of Oncology, The University of Melbourne, Victoria, Australia.

Abstract

AIM:

To examine whether peripheral blood methylation is associated with risk of developing mature B-cell neoplasms (MBCNs).

MATERIALS & METHODS:

We conducted a case-control study nested within a large prospective cohort. Peripheral blood was collected from healthy participants. Cases of MBCN were identified by linkage to cancer registries. Methylation was measured using the Infinium(®) HumanMethylation450.

RESULTS:

During a median of 10.6-year follow-up, 438 MBCN cases were evaluated. Global hypomethylation was associated with increased risk of MBCN (odds ratio: 2.27, [95% CI: 1.59-3.25]). Within high CpG promoter regions, hypermethylation was associated with increased risk (odds ratio: 1.76 [95% CI: 1.25-2.48]). Promoter hypermethylation was observed in HOXA9 and CDH1 genes.

CONCLUSION:

Aberrant global DNA methylation is detectable in peripheral blood collected years before diagnosis and is associated with increased risk of MBCN, suggesting changes to DNA methylation are an early event in MBCN development.

KEYWORDS:

B-cell neoplasms; DNA methylation; lymphoma; peripheral blood methylation

PMID:
26679037
DOI:
10.2217/epi.15.97
[Indexed for MEDLINE]

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