title: Genome-Wide Measures of Peripheral Blood Dna Methylation and Prostate Cancer Risk in a Prospective Nested Case-Control Study.
abstract: Global measures of peripheral blood DNA methylation have been associated with risk of some malignancies, including breast, bladder, and gastric cancer. Here, we examined genome-wide measures of peripheral blood DNA methylation in prostate cancer and its non-aggressive and aggressive disease forms.
  
  
  
  We used a matched, case-control study of 687 incident prostate cancer samples, nested within a larger prospective cohort study. DNA methylation was measured in pre-diagnostic, peripheral blood samples using the Illumina Infinium HM450K BeadChip. Genome-wide measures of DNA methylation were computed as the median M-value of all CpG sites and according to CpG site location and regulatory function. We used conditional logistic regression to test for associations between genome-wide measures of DNA methylation and risk of prostate cancer and its subtypes, and by time between blood draw and diagnosis.
  
  
  
  We observed no associations between the genome-wide measure of DNA methylation based on all CpG sites and risk of prostate cancer or aggressive disease. Risk of non-aggressive disease was associated with higher methylation of CpG islands (OR = 0.80; 95%CI = 0.68-0.94), promoter regions (OR = 0.79; 95%CI = 0.66-0.93), and high density CpG regions (OR = 0.80; 95%CI = 0.68-0.94). Additionally, higher methylation of all CpGs (OR = 0.66; 95%CI = 0.48-0.89), CpG shores (OR = 0.62; 95%CI = 0.45-0.84), and regulatory regions (OR = 0.68; 95% CI = 0.51-0.91) was associated with a reduced risk of overall prostate cancer within 5 years of blood draw but not thereafter.
  
  
  
  A reduced risk of overall prostate cancer within 5 years of blood draw and non-aggressive prostate cancer was associated with higher genome-wide methylation of peripheral blood DNA. While these data have no immediate clinical utility, with further work they may provide insight into the early events of prostate carcinogenesis. Prostate 77:471-478, 2017. © 2017 Wiley Periodicals, Inc.
authors.affiliation: Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, VIC, Australia.|Cancer, Genetics, and Immunology, Menzies Institute for Medical Research, University of Tasmania, Hobart, TAS, Australia.
authors.forename: Liesel M
authors.initials: LM
authors.lastname: FitzGerald
authors.affiliation: Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne, Parkville, VIC, Australia.
authors.forename: Haroon
authors.initials: H
authors.lastname: Naeem
authors.affiliation: Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne, Parkville, VIC, Australia.
authors.forename: Enes
authors.initials: E
authors.lastname: Makalic
authors.affiliation: Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne, Parkville, VIC, Australia.
authors.forename: Daniel F
authors.initials: DF
authors.lastname: Schmidt
authors.affiliation: Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne, Parkville, VIC, Australia.
authors.forename: James G
authors.initials: JG
authors.lastname: Dowty
authors.affiliation: Genetic Epidemiology Laboratory, Department of Pathology, University of Melbourne, Parkville, VIC, Australia.
authors.forename: Jihoon E
authors.initials: JE
authors.lastname: Joo
authors.affiliation: VLSCI Life Sciences Computation Centre, University of Melbourne, Carlton, VIC, Australia.
authors.forename: Chol-Hee
authors.initials: CH
authors.lastname: Jung
authors.affiliation: Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, VIC, Australia.
authors.forename: Julie K
authors.initials: JK
authors.lastname: Bassett
authors.affiliation: Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, VIC, Australia.
authors.forename: Pierre-Antoine
authors.initials: PA
authors.lastname: Dugue
authors.affiliation: VLSCI Life Sciences Computation Centre, University of Melbourne, Carlton, VIC, Australia.
authors.forename: Jessica
authors.initials: J
authors.lastname: Chung
authors.affiliation: VLSCI Life Sciences Computation Centre, University of Melbourne, Carlton, VIC, Australia.
authors.forename: Andrew
authors.initials: A
authors.lastname: Lonie
authors.affiliation: Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, VIC, Australia.|Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne, Parkville, VIC, Australia.
authors.forename: Roger L
authors.initials: RL
authors.lastname: Milne
authors.affiliation: Genetic Epidemiology Laboratory, Department of Pathology, University of Melbourne, Parkville, VIC, Australia.
authors.forename: Ee Ming
authors.initials: EM
authors.lastname: Wong
authors.affiliation: Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne, Parkville, VIC, Australia.
authors.forename: John L
authors.initials: JL
authors.lastname: Hopper
authors.affiliation: Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, VIC, Australia.|Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne, Parkville, VIC, Australia.
authors.forename: Dallas R
authors.initials: DR
authors.lastname: English
authors.affiliation: Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, VIC, Australia.|Université Paris-Saclay, University of Paris-Sud, UVSQ, CESP, INSERM, Villejuif, France.|Gustave Roussy, F-94805, Villejuif, France.|HuGeF, Human Genetics Foundation, Torino, Italy.
authors.forename: Gianluca
authors.initials: G
authors.lastname: Severi
authors.affiliation: Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, VIC, Australia.|Université Paris-Saclay, University of Paris-Sud, UVSQ, CESP, INSERM, Villejuif, France.
authors.forename: Laura
authors.initials: L
authors.lastname: Baglietto
authors.affiliation: TissuPath, Mount Waverley, Melbourne, VIC, Australia.
authors.forename: John
authors.initials: J
authors.lastname: Pedersen
authors.affiliation: Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, VIC, Australia.|Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne, Parkville, VIC, Australia.
authors.forename: Graham G
authors.initials: GG
authors.lastname: Giles
authors.affiliation: Genetic Epidemiology Laboratory, Department of Pathology, University of Melbourne, Parkville, VIC, Australia.
authors.forename: Melissa C
authors.initials: MC
authors.lastname: Southey
mesh_terms: D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D015331:Cohort Studies; D018899:CpG Islands / Q000502:physiology*; D019175:DNA Methylation / Q000502:physiology*; D055106:Genome-Wide Association Study / Q000379:methods*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011471:Prostatic Neoplasms / Q000097:blood* / Q000175:diagnosis / Q000235:genetics*; D012307:Risk Factors
keywords: DNA methylation; HM450K array; biomarker; peripheral blood; prostate cancer