期刊
CANCER CAUSES & CONTROL
卷 22, 期 3, 页码 437-447出版社
SPRINGER
DOI: 10.1007/s10552-010-9715-2
关键词
Repetitive elements; DNA methylation; Epigenetics; Blood; Cancer risk
资金
- National Institute of Environmental Health Sciences [ES015172-01]
- HSPH-NIEHS Center for Environmental Health [ES000002]
- Environmental Protection Agency [R83241601, R827353]
- Italian Association for Cancer Research [AIRC-6016]
- Cooperative Studies Program/Epidemiology Research and Information Center of the U.S. Department of Veterans Affairs and is a component of the Massachusetts Veterans Epidemiology Research and Information Center (MAVERIC)
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.
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