caa a22 4500 445315369 CHVBK 20180317142645.0 cr unu---uuuuu 170323e20110301xx s 000 0 eng 10.1007/s10552-010-9715-2 doi (NATIONALLICENCE)springer-10.1007/s10552-010-9715-2 Repetitive element hypomethylation in blood leukocyte DNA and cancer incidence, prevalence, and mortality in elderly individuals: the Normative Aging Study [Elektronische Daten] [Zhong-Zheng Zhu, David Sparrow, Lifang Hou, Letizia Tarantini, Valentina Bollati, Augusto Litonjua, Antonella Zanobetti, Pantel Vokonas, Robert Wright, Andrea Baccarelli, Joel Schwartz] 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: 89months), prevalence (205 baseline cases), and mortality (28 deaths, median follow-up: 85months). 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. Springer Science+Business Media B.V., 2010 Repetitive elements nationallicence DNA methylation nationallicence Epigenetics nationallicence Blood nationallicence Cancer risk nationallicence Zhu Zhong-Zheng Center of Molecular and Genetic Epidemiology, Department of Environmental and Occupational Health, Università degli Studi di Milano and IRCCS Maggiore Policlinico Hospital, Mangiagalli and Regina Elena Foundation, Milan, Italy aut Sparrow David VA Normative Aging Study, Veterans Affairs Boston Healthcare System and the Department of Medicine, Boston University School of Medicine, Boston, MA, USA aut Hou Lifang Department of Preventive Medicine & Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA aut Tarantini Letizia Center of Molecular and Genetic Epidemiology, Department of Environmental and Occupational Health, Università degli Studi di Milano and IRCCS Maggiore Policlinico Hospital, Mangiagalli and Regina Elena Foundation, Milan, Italy aut Bollati Valentina Center of Molecular and Genetic Epidemiology, Department of Environmental and Occupational Health, Università degli Studi di Milano and IRCCS Maggiore Policlinico Hospital, Mangiagalli and Regina Elena Foundation, Milan, Italy aut Litonjua Augusto Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA aut Zanobetti Antonella Exposure Epidemiology and Risk Program, Harvard School of Public Health, Landmark Center, Suite 415, 401 Park Drive, 02215, Boston, MA, USA aut Vokonas Pantel VA Normative Aging Study, Veterans Affairs Boston Healthcare System and the Department of Medicine, Boston University School of Medicine, Boston, MA, USA aut Wright Robert Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA aut Baccarelli Andrea Center of Molecular and Genetic Epidemiology, Department of Environmental and Occupational Health, Università degli Studi di Milano and IRCCS Maggiore Policlinico Hospital, Mangiagalli and Regina Elena Foundation, Milan, Italy aut Schwartz Joel Exposure Epidemiology and Risk Program, Harvard School of Public Health, Landmark Center, Suite 415, 401 Park Drive, 02215, Boston, MA, USA aut Cancer Causes & Control Springer Netherlands 22/3(2011-03-01), 437-447 0957-5243 22:3<437 2011 22 10552 https://doi.org/10.1007/s10552-010-9715-2 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s10552-010-9715-2 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Zhu Zhong-Zheng Center of Molecular and Genetic Epidemiology, Department of Environmental and Occupational Health, Università degli Studi di Milano and IRCCS Maggiore Policlinico Hospital, Mangiagalli and Regina Elena Foundation, Milan, Italy aut NATIONALLICENCE 700 1- Sparrow David VA Normative Aging Study, Veterans Affairs Boston Healthcare System and the Department of Medicine, Boston University School of Medicine, Boston, MA, USA aut NATIONALLICENCE 700 1- Hou Lifang Department of Preventive Medicine & Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA aut NATIONALLICENCE 700 1- Tarantini Letizia Center of Molecular and Genetic Epidemiology, Department of Environmental and Occupational Health, Università degli Studi di Milano and IRCCS Maggiore Policlinico Hospital, Mangiagalli and Regina Elena Foundation, Milan, Italy aut NATIONALLICENCE 700 1- Bollati Valentina Center of Molecular and Genetic Epidemiology, Department of Environmental and Occupational Health, Università degli Studi di Milano and IRCCS Maggiore Policlinico Hospital, Mangiagalli and Regina Elena Foundation, Milan, Italy aut NATIONALLICENCE 700 1- Litonjua Augusto Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA aut NATIONALLICENCE 700 1- Zanobetti Antonella Exposure Epidemiology and Risk Program, Harvard School of Public Health, Landmark Center, Suite 415, 401 Park Drive, 02215, Boston, MA, USA aut NATIONALLICENCE 700 1- Vokonas Pantel VA Normative Aging Study, Veterans Affairs Boston Healthcare System and the Department of Medicine, Boston University School of Medicine, Boston, MA, USA aut NATIONALLICENCE 700 1- Wright Robert Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA aut NATIONALLICENCE 700 1- Baccarelli Andrea Center of Molecular and Genetic Epidemiology, Department of Environmental and Occupational Health, Università degli Studi di Milano and IRCCS Maggiore Policlinico Hospital, Mangiagalli and Regina Elena Foundation, Milan, Italy aut NATIONALLICENCE 700 1- Schwartz Joel Exposure Epidemiology and Risk Program, Harvard School of Public Health, Landmark Center, Suite 415, 401 Park Drive, 02215, Boston, MA, USA aut NATIONALLICENCE 773 0- Cancer Causes & Control Springer Netherlands 22/3(2011-03-01), 437-447 0957-5243 22:3<437 2011 22 10552 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer