title: Genome-wide measures of DNA methylation in peripheral blood and the risk of urothelial cell carcinoma: a prospective nested case-control study.
abstract: Global DNA methylation has been reported to be associated with urothelial cell carcinoma (UCC) by studies using blood samples collected at diagnosis. Using the Illumina HumanMethylation450 assay, we derived genome-wide measures of blood DNA methylation and assessed them for their prospective association with UCC risk.
  
  
  
  We used 439 case-control pairs from the Melbourne Collaborative Cohort Study matched on age, sex, country of birth, DNA sample type, and collection period. Conditional logistic regression was used to compute odds ratios (OR) of UCC risk per s.d. of each genome-wide measure of DNA methylation and 95% confidence intervals (CIs), adjusted for potential confounders. We also investigated associations by disease subtype, sex, smoking, and time since blood collection.
  
  
  
  The risk of superficial UCC was decreased for individuals with higher levels of our genome-wide DNA methylation measure (OR=0.71, 95% CI: 0.54-0.94; P=0.02). This association was particularly strong for current smokers at sample collection (OR=0.47, 95% CI: 0.27-0.83). Intermediate levels of our genome-wide measure were associated with decreased risk of invasive UCC. Some variation was observed between UCC subtypes and the location and regulatory function of the CpGs included in the genome-wide measures of methylation.
  
  
  
  Higher levels of our genome-wide DNA methylation measure were associated with decreased risk of superficial UCC and intermediate levels were associated with reduced risk of invasive disease. These findings require replication by other prospective studies.
authors.affiliation: Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, VIC 3004, Australia.|Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne, Parkville, VIC 3052, Australia.
authors.forename: Pierre-Antoine
authors.initials: PA
authors.lastname: Dugué
authors.affiliation: Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, VIC 3004, Australia.
authors.forename: Maree T
authors.initials: MT
authors.lastname: Brinkman
authors.affiliation: Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, VIC 3004, Australia.|Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne, Parkville, VIC 3052, Australia.
authors.forename: Roger L
authors.initials: RL
authors.lastname: Milne
authors.affiliation: Genetic Epidemiology Laboratory, Department of Pathology, University of Melbourne, Parkville, VIC 3052, Australia.
authors.forename: Ee Ming
authors.initials: EM
authors.lastname: Wong
authors.affiliation: Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, VIC 3004, Australia.|Menzies Institute for Medical Research, University of Tasmania, Hobart, TAS 7000, Australia.
authors.forename: Liesel M
authors.initials: LM
authors.lastname: FitzGerald
authors.affiliation: Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, VIC 3004, Australia.
authors.forename: Julie K
authors.initials: JK
authors.lastname: Bassett
authors.affiliation: Genetic Epidemiology Laboratory, Department of Pathology, University of Melbourne, Parkville, VIC 3052, Australia.
authors.forename: Jihoon E
authors.initials: JE
authors.lastname: Joo
authors.affiliation: VLSCI Life Sciences Computation Centre, University of Melbourne, Carlton, VIC 3053, Australia.
authors.forename: Chol-Hee
authors.initials: CH
authors.lastname: Jung
authors.affiliation: Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne, Parkville, VIC 3052, 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 3052, Australia.
authors.forename: Daniel F
authors.initials: DF
authors.lastname: Schmidt
authors.affiliation: Genetic Epidemiology Laboratory, Department of Pathology, University of Melbourne, Parkville, VIC 3052, Australia.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Park
authors.affiliation: Menzies Institute for Medical Research, University of Tasmania, Hobart, TAS 7000, Australia.
authors.forename: Jessica
authors.initials: J
authors.lastname: Chung
authors.affiliation: Department of Surgery, University of Melbourne, Melbourne, VIC 3004, Australia.
authors.forename: Anthony D
authors.initials: AD
authors.lastname: Ta
authors.affiliation: Department of Surgery, University of Melbourne, Melbourne, VIC 3004, Australia.
authors.forename: Damien M
authors.initials: DM
authors.lastname: Bolton
authors.affiliation: VLSCI Life Sciences Computation Centre, University of Melbourne, Carlton, VIC 3053, Australia.
authors.forename: Andrew
authors.initials: A
authors.lastname: Lonie
authors.affiliation: Department of Anatomical Pathology, Monash Medical Centre, Clayton, VIC 3800, Australia.
authors.forename: Anthony
authors.initials: A
authors.lastname: Longano
authors.affiliation: Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne, Parkville, VIC 3052, Australia.
authors.forename: John L
authors.initials: JL
authors.lastname: Hopper
authors.affiliation: Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, VIC 3004, Australia.|Université Paris-Saclay, Univ. Paris-Sud, UVSQ, CESP, INSERM, Villejuif, France.|Gustave Roussy, Villejuif F-94805, France.|HuGeF, Human Genetics Foundation, Torino 10126, Italy.
authors.forename: Gianluca
authors.initials: G
authors.lastname: Severi
authors.affiliation: Department of Paediatrics, University of Melbourne, Melbourne, VIC, Australia.|Cancer, Disease and Developmental Epigenetics Group, Cell Biology, Development and Disease Theme, Murdoch Childrens Research Institute, Royal Children's Hospital, Melbourne, VIC, Australia.
authors.forename: Richard
authors.initials: R
authors.lastname: Saffery
authors.affiliation: Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, VIC 3004, Australia.|Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne, Parkville, VIC 3052, Australia.
authors.forename: Dallas R
authors.initials: DR
authors.lastname: English
authors.affiliation: Genetic Epidemiology Laboratory, Department of Pathology, University of Melbourne, Parkville, VIC 3052, Australia.
authors.forename: Melissa C
authors.initials: MC
authors.lastname: Southey
authors.affiliation: Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, VIC 3004, Australia.|Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne, Parkville, VIC 3052, Australia.
authors.forename: Graham G
authors.initials: GG
authors.lastname: Giles
mesh_terms: D000328:Adult; D000368:Aged; D001800:Blood Specimen Collection; D002295:Carcinoma, Transitional Cell / Q000097:blood / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D016022:Case-Control Studies; D018899:CpG Islands; D004247:DNA / Q000097:blood*; D019175:DNA Methylation; D004032:Diet; D005260:Female; D005500:Follow-Up Studies; D055106:Genome-Wide Association Study; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D011446:Prospective Studies; D012306:Risk; D012307:Risk Factors; D012907:Smoking / Q000453:epidemiology; D013997:Time Factors; D014571:Urologic Neoplasms / Q000097:blood / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D014739:Victoria / Q000453:epidemiology
chemical_list: D004247:DNA