title: Prospective study of DNA methylation at LINE-1 and Alu in peripheral blood and the risk of prostate cancer.
abstract: BACKGROUND
  Evidence suggests that global blood DNA methylation levels may be associated with the risk of various cancers, but no studies have evaluated this relationship for prostate cancer.
  
  
  METHODS
  We used pyrosequencing to quantify DNA methylation levels at the long interspersed nuclear element 1 (LINE-1) and Alu repetitive elements in pre-diagnostic blood samples from 694 prostate cancer cases and 703 controls from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. We evaluated prostate cancer risk associated with the mean methylation level for each element using logistic regression, adjusting for potential confounders.
  
  
  RESULTS
  We did not observe a significant association with prostate cancer for LINE-1 [odds ratio (OR) for the highest compared to the lowest quartile = 1.01, 95% confidence interval (CI): 0.73-1.39, Ptrend  = 0.99] or Alu (OR = 0.94, 95% CI: 0.68-1.29, Ptrend  = 0.69) methylation levels overall. However, for Alu, we observed that higher DNA methylation levels were associated with a significant increased risk for those diagnosed 4 or more years after blood draw (OR = 2.26, 95% CI: 1.27-4.00, Ptrend  = 4.4 × 10(-3) ). In contrast, there was no association for those diagnosed 2 (OR = 1.13, 95% CI: 0.67-1.90, Ptrend  = 0.64) or 3 years after draw (OR = 1.22, 95% CI: 0.71-2.07, Ptrend  = 0.32), and a decreased risk for those diagnosed less than 2 years after draw (OR = 0.40, 95% CI: 0.25-0.65, Ptrend  = 3.8 × 10(-5) ; Pheterogeneity  = 5.3 × 10(-6) ).
  
  
  CONCLUSIONS
  Although LINE-1 DNA methylation levels were not associated with prostate cancer, we observed an association for Alu that varied by time from blood draw to diagnosis. Our study suggests that elevated Alu blood DNA methylation levels several years before diagnosis may be associated with an increased prostate cancer risk.
authors.affiliation: Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland.
authors.forename: Kathryn Hughes
authors.initials: KH
authors.lastname: Barry
authors.affiliation: Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland.
authors.forename: Lee E
authors.initials: LE
authors.lastname: Moore
authors.affiliation: Nutritional Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland.
authors.forename: Linda M
authors.initials: LM
authors.lastname: Liao
authors.affiliation: Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland.
authors.forename: Wen-Yi
authors.initials: WY
authors.lastname: Huang
authors.affiliation: Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Andreotti
authors.affiliation: EpigenDx, Inc., Hopkinton, Massachusetts.
authors.forename: Matthew
authors.initials: M
authors.lastname: Poulin
authors.affiliation: Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland.
authors.forename: Sonja I
authors.initials: SI
authors.lastname: Berndt
mesh_terms: D000368:Aged; D020087:Alu Elements / Q000235:genetics*; D016022:Case-Control Studies; D019175:DNA Methylation; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D020084:Long Interspersed Nucleotide Elements / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011471:Prostatic Neoplasms / Q000097:blood / Q000235:genetics* / Q000473:pathology; D012306:Risk
keywords: global DNA methylation; pre-diagnostic; prostate cancer; repetitive element