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

Nicole Wong Doo, Enes Makalic, Jihoon E. Joo, Claire M. Vajdic, Daniel F. Schmidt, Ee Ming Wong, Chol-Hee Jung, Gianluca Severi, Daniel J. Park, Jessica Chung, Laura Baglietto, Henry Miles Prince, John F. Seymour, Constantine Tam, John L. Hopper, Dallas R. English, Roger L. Milne, Simon J. Harrison, Melissa C. Southey, Graham G. Giles

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22 Citations (Scopus)

Abstract

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

Original languageEnglish
Pages (from-to)55-66
Number of pages12
JournalEpigenomics
Volume8
Issue number1
DOIs
Publication statusPublished - Jan 2016
Externally publishedYes

Keywords

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

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