title: Genomic methylation of leukocyte DNA in relation to colorectal adenoma among asymptomatic women.
abstract: OBJECTIVE
  Systemic inhibition of DNA methylation causes cancers in animals, in part by inducing genetic instability. Epidemiologic evidence linking low genomic methylation in systemic blood DNA to carcinogenesis is limited, however, specifically to the colorectum, in which genetic instability is a primary etiologic factor. We examined genomic methylation of leukocyte DNA in relation to colorectal adenoma (CRA) among asymptomatic women (40-79 years of age) participating in a multicenter colonoscopy screening study (CONCeRN Study, 2000-2002).
  
  
  METHODS
  Of all participants who completed self-administered risk factor and food frequency questionnaires, peripheral blood donation, and colonoscopy, 115 pairs of CRA cases and controls with matching age and month of blood draw were studied. Genomic methylation of leukocyte DNA was determined by liquid chromatography mass spectrometry. Conditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI).
  
  
  RESULTS
  Compared with women in the lowest tertile of genomic methylation, women in the second (OR, 0.72; 95% CI: 0.34-1.52) and third tertiles (OR, 0.17; 95% CI: 0.06-0.49) had lower risk of CRA (P trend = .002). The inverse relationship was stronger for nonadvanced than for advanced adenoma and, less notably, for proximal than for distal adenoma. The association was also moderately more protective with low rather than high total folate intake but did not differ by other nutrients involved in 1-carbon metabolism or colorectal cancer risk factors.
  
  
  CONCLUSIONS
  Our findings regarding asymptomatic CRA implicate systemic genomic methylation as a potential etiologic factor for an early stage of CRA.
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Rockville, Maryland, USA.
authors.forename: Unhee
authors.initials: U
authors.lastname: Lim
authors.forename: Andrew
authors.initials: A
authors.lastname: Flood
authors.forename: Sang-Woon
authors.initials: SW
authors.lastname: Choi
authors.forename: Demetrius
authors.initials: D
authors.lastname: Albanes
authors.forename: Amanda J
authors.initials: AJ
authors.lastname: Cross
authors.forename: Arthur
authors.initials: A
authors.lastname: Schatzkin
authors.forename: Rashmi
authors.initials: R
authors.lastname: Sinha
authors.forename: Hormuzd A
authors.initials: HA
authors.lastname: Katki
authors.forename: Brooks
authors.initials: B
authors.lastname: Cash
authors.forename: Phillip
authors.initials: P
authors.lastname: Schoenfeld
authors.forename: Rachael
authors.initials: R
authors.lastname: Stolzenberg-Solomon
mesh_terms: D000236:Adenoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D015331:Cohort Studies; D003113:Colonoscopy; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D019175:DNA Methylation; D005260:Female; D006801:Humans; D007962:Leukocytes / Q000502:physiology*; D008019:Life Style; D008875:Middle Aged; D009752:Nutritional Status; D012307:Risk Factors; D014481:United States