title: Global measures of peripheral blood-derived DNA methylation as a risk factor in the development of mature B-cell neoplasms.
abstract: OBJECTIVE
  To examine whether peripheral blood methylation is associated with risk of developing mature B-cell neoplasms (MBCNs).
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Cancer Epidemiology Centre, Cancer Council Victoria, Australia.|Concord General & Repatriation Hospital, NSW, Australia.
authors.forename: Nicole
authors.initials: N
authors.lastname: Wong Doo
authors.affiliation: Centre for Epidemiology & Biostatistics, The University of Melbourne, Victoria, Australia.
authors.forename: Enes
authors.initials: E
authors.lastname: Makalic
authors.affiliation: Department of Pathology, The University of Melbourne, Victoria, Australia.
authors.forename: JiHoon E
authors.initials: JE
authors.lastname: Joo
authors.affiliation: Centre for Big Data Research in Health, University of New South Wales, Australia.
authors.forename: Claire M
authors.initials: CM
authors.lastname: Vajdic
authors.affiliation: Centre for Epidemiology & Biostatistics, The University of Melbourne, Victoria, Australia.
authors.forename: Daniel F
authors.initials: DF
authors.lastname: Schmidt
authors.affiliation: Department of Pathology, The University of Melbourne, Victoria, Australia.
authors.forename: Ee Ming
authors.initials: EM
authors.lastname: Wong
authors.affiliation: VLSCI Life Sciences Computation Centre, The University of Melbourne, Victoria, Australia.
authors.forename: Chol-Hee
authors.initials: CH
authors.lastname: Jung
authors.affiliation: Human Genetics Foundation, Torino, Italy.
authors.forename: Gianluca
authors.initials: G
authors.lastname: Severi
authors.affiliation: Department of Pathology, The University of Melbourne, Victoria, Australia.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Park
authors.affiliation: VLSCI Life Sciences Computation Centre, The University of Melbourne, Victoria, Australia.
authors.forename: Jessica
authors.initials: J
authors.lastname: Chung
authors.affiliation: Cancer Epidemiology Centre, Cancer Council Victoria, Australia.|Centre for Epidemiology & Biostatistics, The University of Melbourne, Victoria, Australia.
authors.forename: Laura
authors.initials: L
authors.lastname: Baglietto
authors.affiliation: Department of Haematology, Peter MacCallum Cancer Centre, Victoria, Australia.|Sir Peter MacCallum Department of Oncology, The University of Melbourne, Victoria, Australia.
authors.forename: Henry Miles
authors.initials: HM
authors.lastname: Prince
authors.affiliation: Department of Haematology, Peter MacCallum Cancer Centre, Victoria, Australia.|Sir Peter MacCallum Department of Oncology, The University of Melbourne, Victoria, Australia.
authors.forename: John F
authors.initials: JF
authors.lastname: Seymour
authors.affiliation: Department of Haematology, Peter MacCallum Cancer Centre, Victoria, Australia.
authors.forename: Constantine
authors.initials: C
authors.lastname: Tam
authors.affiliation: Centre for Epidemiology & Biostatistics, The University of Melbourne, Victoria, Australia.
authors.forename: John L
authors.initials: JL
authors.lastname: Hopper
authors.affiliation: Cancer Epidemiology Centre, Cancer Council Victoria, Australia.|Centre for Epidemiology & Biostatistics, The University of Melbourne, Victoria, Australia.
authors.forename: Dallas R
authors.initials: DR
authors.lastname: English
authors.affiliation: Cancer Epidemiology Centre, Cancer Council Victoria, Australia.|Centre for Epidemiology & Biostatistics, The University of Melbourne, Victoria, Australia.
authors.forename: Roger L
authors.initials: RL
authors.lastname: Milne
authors.affiliation: Department of Haematology, Peter MacCallum Cancer Centre, Victoria, Australia.
authors.forename: Simon J
authors.initials: SJ
authors.lastname: Harrison
authors.affiliation: Department of Pathology, The University of Melbourne, Victoria, Australia.
authors.forename: Melissa C
authors.initials: MC
authors.lastname: Southey
authors.affiliation: Cancer Epidemiology Centre, Cancer Council Victoria, Australia.|Centre for Epidemiology & Biostatistics, The University of Melbourne, Victoria, Australia.
authors.forename: Graham G
authors.initials: GG
authors.lastname: Giles
mesh_terms: D000328:Adult; D000368:Aged; D015703:Antigens, CD; D001402:B-Lymphocytes / Q000473:pathology*; D015820:Cadherins / Q000097:blood* / Q000235:genetics*; D016022:Case-Control Studies; D018899:CpG Islands; D019175:DNA Methylation; D005260:Female; D020022:Genetic Predisposition to Disease; D018398:Homeodomain Proteins / Q000097:blood / Q000235:genetics*; D006801:Humans; D008232:Lymphoproliferative Disorders / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011401:Promoter Regions, Genetic; D011446:Prospective Studies; D000091363:Protocadherins
chemical_list: D015703:Antigens, CD; C513384:CDH1 protein, human; D015820:Cadherins; D018398:Homeodomain Proteins; C438603:PCDH10 protein, human; D000091363:Protocadherins; C097899:homeobox protein HOXA9
keywords: B-cell neoplasms; DNA methylation; lymphoma; peripheral blood methylation