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Leukocyte-adjusted epigenome-wide association studies of blood from solid tumor patients.
MedLine Citation:
PMID:  24671036     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Epigenome-wide studies of DNA methylation using blood-derived DNA from cancer patients are complicated by the heterogeneity of cell types within blood and the associated cell lineage specification of DNA methylation signatures. Here, we applied a novel set of analytic approaches to assess the association between cancer case-status and DNA methylation adjusted for leukocyte variation using blood specimens from three case-control cancer studies (bladder: 223 cases, 205 controls; head and neck: 92 cases, 92 controls; and ovarian: 131 cases, 274 controls). Using previously published data on leukocyte-specific CpG loci and a recently described approach to deconvolute subject-specific blood composition, we performed an epigenome-wide analysis to examine the association between blood-based DNA methylation patterns and each of the three aforementioned solid tumor types adjusted for cellular heterogeneity in blood. After adjusting for leukocyte profile in our epigenome-wide analysis, the omnibus association between case-status and methylation was significant for all three studies (bladder cancer: P = 0.047; HNSCC: P = 0.013; ovarian cancer: P = 0.0002). Subsequent analyses revealed that CpG sites associated with cancer were enriched for transcription factor binding motifs involved with cancer-associated pathways. These results support the existence of cancer-associated DNA methylation profiles in the blood of solid tumor patients that are independent of alterations in normal leukocyte distributions. Adoption of the methods developed here will make it feasible to rigorously assess the influence of variability of normal leukocyte profiles when investigating cancer related changes in blood-based epigenome-wide association studies.
Authors:
Scott M Langevin; E Andres Houseman; William P Accomando; Devin C Koestler; Brock C Christensen; Heather H Nelson; Margaret R Karagas; Carmen J Marsit; John K Wiencke; Karl T Kelsey
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-3-26
Journal Detail:
Title:  Epigenetics : official journal of the DNA Methylation Society     Volume:  9     ISSN:  1559-2308     ISO Abbreviation:  Epigenetics     Publication Date:  2014 Mar 
Date Detail:
Created Date:  2014-3-27     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101265293     Medline TA:  Epigenetics     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
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