title: Pre-diagnostic leukocyte genomic DNA methylation and the risk of colorectal cancer in women.
abstract: BACKGROUND
  Abnormal one-carbon metabolism may lead to general genomic (global) hypomethylation, which may predispose an individual to the development of colorectal neoplasia.
  
  
  METHODS
  We evaluated the association between pre-diagnostic leukocyte genomic DNA methylation level and the risk of colorectal cancer in a nested case-control study of 358 colorectal cancer cases and 661 matched controls within the all-female cohort of the Nurses' Health Study (NHS). Among control subjects, we further examined major plasma components in the one-carbon metabolism pathway in relation to genomic DNA methylation level. Liquid chromatography/tandem mass spectrometry was used to examine leukocyte genomic DNA methylation level. We calculated odds ratios (ORs) and 95% confidence intervals (95% CIs) using logistic regression.
  
  
  RESULTS
  Overall genomic DNA methylation level was not associated with the risk of colorectal cancer (p for trend, 0.45). Compared with women in the lowest quintile of methylation, the multivariate OR of colorectal cancer risk was 1.32 (95% CI, 0.82-2.13) for those in the highest quintile. We did not find significant associations between major plasma components of one-carbon metabolism or risk factors for colorectal cancer and genomic DNA methylation level (all p for trend >0.05). Also, neither one-carbon metabolism-related plasma components nor well-known risk factors for colorectal cancer modified the association between genomic DNA methylation level and the risk of colorectal cancer (all p for interaction >0.05).
  
  
  CONCLUSIONS
  We found no evidence that hypomethylation of leukocyte genomic DNA increases risk of colorectal cancer among women. Additional studies are needed to investigate the association between pre-diagnostic genomic DNA methylation level and colorectal cancer risk among diverse populations.
authors.affiliation: Division of Cancer Epidemiology, Department of Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore, MD, USA.
authors.forename: Hongmei
authors.initials: H
authors.lastname: Nan
authors.forename: Edward L
authors.initials: EL
authors.lastname: Giovannucci
authors.forename: Kana
authors.initials: K
authors.lastname: Wu
authors.forename: Jacob
authors.initials: J
authors.lastname: Selhub
authors.forename: Ligi
authors.initials: L
authors.lastname: Paul
authors.forename: Bernard
authors.initials: B
authors.lastname: Rosner
authors.forename: Charles S
authors.initials: CS
authors.lastname: Fuchs
authors.forename: Eunyoung
authors.initials: E
authors.lastname: Cho
mesh_terms: D000230:Adenocarcinoma / Q000097:blood* / Q000235:genetics / Q000473:pathology; D000328:Adult; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000097:blood* / Q000235:genetics / Q000473:pathology; D003545:Cysteine / Q000097:blood; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006306:Health Surveys; D006710:Homocysteine / Q000097:blood; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism* / Q000473:pathology; D016015:Logistic Models; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000097:blood / Q000235:genetics; D008875:Middle Aged; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D011732:Pyridoxal Phosphate / Q000097:blood; D012307:Risk Factors
chemical_list: D004273:DNA, Neoplasm; D006710:Homocysteine; D011732:Pyridoxal Phosphate; C573423:MTHFR protein, human; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D003545:Cysteine
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