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.
Repetitive element hypomethylation in blood leukocyte DNA and cancer incidence, prevalence, and mortality in elderly individuals : the Normative Aging Study / Z.Z. Zhu, D. Sparrow, L. Hou, L. Tarantini, V. Bollati, A.A. Litonjua, A. Zanobetti, P. Vokonas, R.O. Wright, A. Baccarelli, J. Schwartz. - In: CANCER CAUSES & CONTROL. - ISSN 0957-5243. - 22:3(2011 Mar), pp. 437-447.
|Titolo:||Repetitive element hypomethylation in blood leukocyte DNA and cancer incidence, prevalence, and mortality in elderly individuals : the Normative Aging Study|
BACCARELLI, ANDREA (Penultimo)
|Parole Chiave:||Blood; Cancer risk; DNA methylation; Epigenetics; Repetitive elements|
|Settore Scientifico Disciplinare:||Settore MED/44 - Medicina del Lavoro|
|Data di pubblicazione:||mar-2011|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1007/s10552-010-9715-2|
|Appare nelle tipologie:||01 - Articolo su periodico|