title: DNA methylation array analysis identifies profiles of blood-derived DNA methylation associated with bladder cancer.
abstract: OBJECTIVE
  Epigenetic alterations in tissues targeted for cancer play a causal role in carcinogenesis. Changes in DNA methylation in nontarget tissues, specifically peripheral blood, can also affect risk of malignant disease. We sought to identify specific profiles of DNA methylation in peripheral blood that are associated with bladder cancer risk and therefore serve as an epigenetic marker of disease susceptibility.
  
  
  METHODS
  We performed genome-wide DNA methylation profiling on participants involved in a population-based incident case-control study of bladder cancer.
  
  
  RESULTS
  In a training set of 112 cases and 118 controls, we identified a panel of 9 CpG loci whose profile of DNA methylation was significantly associated with bladder cancer in a masked, independent testing series of 111 cases and 119 controls (P < .0001). Membership in three of the most methylated classes was associated with a 5.2-fold increased risk of bladder cancer (95% CI, 2.8 to 9.7), and a model that included the methylation classification, participant age, sex, smoking status, and family history of bladder cancer was a significant predictor of bladder cancer (area under the curve, 0.76; 95% CI, 0.70 to 0.82). CpG loci associated with bladder cancer and aging had neighboring sequences enriched for transcription-factor binding sites related to immune modulation and forkhead family members.
  
  
  CONCLUSIONS
  These results indicate that profiles of epigenetic states in blood are associated with risk of bladder cancer and signal the potential utility of epigenetic profiles in peripheral blood as novel markers of susceptibility to this and other malignancies.
authors.affiliation: Pathology and Laboratory Medicine, Brown University, Providence, RI 02912, USA. carmen_marsit@brown.edu
authors.forename: Carmen J
authors.initials: CJ
authors.lastname: Marsit
authors.forename: Devin C
authors.initials: DC
authors.lastname: Koestler
authors.forename: Brock C
authors.initials: BC
authors.lastname: Christensen
authors.forename: Margaret R
authors.initials: MR
authors.lastname: Karagas
authors.forename: E Andres
authors.initials: EA
authors.lastname: Houseman
authors.forename: Karl T
authors.initials: KT
authors.lastname: Kelsey
mesh_terms: D000328:Adult; D000368:Aged; D002278:Carcinoma in Situ / Q000097:blood / Q000235:genetics / Q000473:pathology; D016022:Case-Control Studies; D018899:CpG Islands / Q000235:genetics*; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000235:genetics*; D057890:Epigenomics; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D011379:Prognosis; D012372:ROC Curve; D001749:Urinary Bladder Neoplasms / Q000097:blood* / Q000235:genetics* / Q000473:pathology
chemical_list: D004273:DNA, Neoplasm