Repetitive element hypomethylation in blood leukocyte DNA and cancer incidence, prevalence, and mortality in elderly individuals: The Normative Aging Study

Zhong Zheng Zhu*, David Sparrow, Lifang Hou, Letizia Tarantini, Valentina Bollati, Augusto A. Litonjua, Antonella Zanobetti, Pantel Vokonas, Robert O. Wright, Andrea Baccarelli, Joel Schwartz

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

60 Scopus citations

Abstract

Background Global genomic hypomethylation is a common epigenetic event in cancer that mostly results from hypomethylation of repetitive DNA elements. Case- control studies have associated blood leukocyte DNA hypomethylation with several cancers. Because samples in case-control studies are collected after disease development, whether DNA hypomethylation is causal or just associated with cancer development is still unclear. Methods In 722 elderly subjects from the Normative Aging Study cohort, we examined whether DNA methylation in repetitive elements (Alu, LINE-1) was associated with cancer incidence (30 new cases, median follow-up: 89 months), prevalence (205 baseline cases), and mortality (28 deaths, median follow-up: 85 months). DNA methylation was measured by bisulfite pyrosequencing. Results Individuals with low LINE-1 methylation (<median) had a 3.0-fold (95%CI 1.3-6.9) increased incidence of all cancers combined. LINE-1 and Alu methylation were not significantly associated with cancer prevalence at baseline (all cancers combined). However, individuals with low LINE-1 methylation (<median) had a 3.2-fold (95% CI 1.4-7.5) higher prevalence of lung cancer. Individuals with low LINE-1 or Alu methylation (<median) had increased cancer mortality (HR = 3.2, 95%CI 1.3-7.9 for LINE-1; HR = 2.5, 95%CI 1.1-5.8 for Alu). Conclusion These findings suggest that individuals with lower repetitive element methylation are at high risk of developing and dying from cancer.

Original languageEnglish (US)
Pages (from-to)437-447
Number of pages11
JournalCancer Causes and Control
Volume22
Issue number3
DOIs
StatePublished - Mar 2011

Keywords

  • Blood
  • Cancer risk
  • DNA methylation
  • Epigenetics
  • Repetitive elements

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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