title: LINE-1 methylation levels in leukocyte DNA and risk of renal cell cancer.
abstract: OBJECTIVE
  Leukocyte global DNA methylation levels are currently being considered as biomarkers of cancer susceptibility and have been associated with risk of several cancers. In this study, we aimed to examine the association between long interspersed nuclear elements (LINE-1) methylation levels, as a biomarker of global DNA methylation in blood cell DNA, and renal cell cancer risk.
  
  
  METHODS
  LINE-1 methylation of bisulfite-converted genomic DNA isolated from leukocytes was quantified by pyrosequencing measured in triplicate, and averaged across 4 CpG sites. A total of 328 RCC cases and 654 controls frequency-matched(2∶1) on age(±5years), sex and study center, from a large case-control study conducted in Central and Eastern Europe were evaluated.
  
  
  RESULTS
  LINE-1 methylation levels were significantly higher in RCC cases with a median of 81.97% (interquartile range[IQR]: 80.84-83.47) compared to 81.67% (IQR: 80.35-83.03) among controls (p = 0.003, Wilcoxon). Compared to the lowest LINE-1 methylation quartile(Q1), the adjusted ORs for increasing methylation quartiles were as follows: OR(Q2) = 1.84(1.20-2.81), OR(Q3) = 1.72(1.11-2.65) and OR(Q4) = 2.06(1.34-3.17), with a p-trend = 0.004. The association was stronger among current smokers (p-trend<0.001) than former or never smokers (p-interaction = 0.03). To eliminate the possibility of selection bias among controls, the relationship between LINE-1 methylation and smoking was evaluated and confirmed in a case-only analysis, as well.
  
  
  CONCLUSIONS
  Higher levels of LINE-1 methylation appear to be positively associated with RCC risk, particularly among current smokers. Further investigations using both post- and pre-diagnostic genomic DNA is warranted to confirm findings and will be necessary to determine whether the observed differences occur prior to, or as a result of carcinogenesis.
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, United States of America. liaolm@mail.nih.gov
authors.forename: Linda M
authors.initials: LM
authors.lastname: Liao
authors.forename: Paul
authors.initials: P
authors.lastname: Brennan
authors.forename: Dana M
authors.initials: DM
authors.lastname: van Bemmel
authors.forename: David
authors.initials: D
authors.lastname: Zaridze
authors.forename: Vsevolod
authors.initials: V
authors.lastname: Matveev
authors.forename: Vladimir
authors.initials: V
authors.lastname: Janout
authors.forename: Hellena
authors.initials: H
authors.lastname: Kollarova
authors.forename: Vladimir
authors.initials: V
authors.lastname: Bencko
authors.forename: Marie
authors.initials: M
authors.lastname: Navratilova
authors.forename: Neonila
authors.initials: N
authors.lastname: Szeszenia-Dabrowska
authors.forename: Dana
authors.initials: D
authors.lastname: Mates
authors.forename: Nathaniel
authors.initials: N
authors.lastname: Rothman
authors.forename: Paolo
authors.initials: P
authors.lastname: Boffetta
authors.forename: Wong-Ho
authors.initials: WH
authors.lastname: Chow
authors.forename: Lee E
authors.initials: LE
authors.lastname: Moore
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood / Q000235:genetics*; D002292:Carcinoma, Renal Cell / Q000097:blood / Q000235:genetics*; D016022:Case-Control Studies; D004247:DNA / Q000097:blood / Q000235:genetics*; D019175:DNA Methylation; D005061:Europe, Eastern; D005260:Female; D006801:Humans; D007680:Kidney Neoplasms / Q000097:blood / Q000235:genetics*; D007962:Leukocytes / Q000378:metabolism* / Q000473:pathology; D020084:Long Interspersed Nucleotide Elements / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D004247:DNA
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