No association between global DNA methylation in peripheral blood and lung cancer risk in nonsmoking women: results from a multicenter study in Eastern and Central Europe Ann Davis a, *, Meng-Hua Tao a,b, *, Jia Chen c , Ghislaine Scelo d , Vladimir Bencko e , Eleonora Fabianova h , Lenka Foretova f , Vladimir Janout g , Jolanta Lissowska i , Dana Mates j , Ioan N. Mates k , Peter Rudnai l , David Zaridze m and Paolo Boffetta b Alterations in global DNA methylation have been suggested to play an important role in cancer development. We evaluated the association of global DNA methylation in peripheral blood with the risk of lung cancer in nonsmoking women from six countries in Central and Eastern Europe. This multicenter case–control study included primary, incident lung cancer cases diagnosed from 1998 to 2001 and controls frequency-matched for geographic area, sex, and age. Global methylation was assessed in peripheral blood DNA from 83 nonsmoking female cases and 181 nonsmoking female controls using the luminometric methylation assay (LUMA). Unconditional logistic regression models were used to estimate associations between DNA methylation in the blood and the risk of lung cancer. LUMA methylation level was not associated with the risk of lung cancer in nonsmoking women. Associations were not significantly different according to different strata of age, BMI, alcohol drinking, or second-hand tobacco smoke exposure status. In our study of nonsmoking women, the LUMA methylation level in peripheral blood was not associated with the risk of lung cancer. Our findings do not support an association of global blood DNA methylation with the risk of lung cancer in nonsmoking women. European Journal of Cancer Prevention 00:000–000 Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved. European Journal of Cancer Prevention 2016, 00:000–000 Keywords: epidemiology, global methylation, lung cancer, never-smoking women a Department of Biostatistics and Epidemiology, University of North Texas Health Science Center, Fort Worth, Texas, b Institute for Translational Epidemiology, c Department of Community and Preventive Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA, d International Agency for Research on Cancer, Lyon, France, e Institute of Hygiene and Epidemiology, First Faculty of Medicine, Charles University in Prague, Prague, f Department of Cancer Epidemiology and Genetics, Masaryk Cancer Institute and Medical Faculty of Masaryk University, Brno, g Department of Preventive Medicine, Palacky University of Medicine, Olomouc, Czech Republic, h Department of Occupational Health, Specialized State Health Institute, Banska Bystrica, Slovakia, i Department of Cancer Epidemiology and Prevention, Cancer Center and M. Sklodowska-Curie Memorial Institute of Oncology, Warsaw, Poland, j Institute of Hygiene, Public Health, Health Services and Management, k General Surgery Department, “St Mary” Clinical Hospital, University of Medicine and Pharmacy ‘Carol Davila’ Bucharest, Romania, l National Institute of Environmental Health, Budapest, Hungary and m Department of Epidemiology and Prevention, Russian N.N. Blokhin Cancer Research Center, Moscow, Russia Correspondence to Meng-Hua Tao, PhD, Department of Biostatistics and Epidemiology, University of North Texas Health Science Center, Fort Worth, TX 76107, USA Tel: + 1 817 735 0520; fax: + 1 817 735 0446; e-mail: menghua.tao@unthsc.edu *Ann Davis and Meng-Hua Tao contributed equally to the writing of this article. Received 3 December 2015 Accepted 7 February 2016 Introduction Identification of potential biomarker for early detection of lung cancer in never smokers is of great public health importance as ∼ 10–25% of lung cancer cases worldwide occur in never smokers (Couraud et al., 2012). It is now widely acknowledged that epigenetic alterations can have various impacts on disease susceptibility and development. Aberrant DNA methylation, an epigenetic modification, plays an important role in lung carcino- genesis (Brennan and Flanagan, 2012). Global DNA hypomethylation has been recognized as an early and important epigenetic alteration in cancer development (Brzeziańska et al., 2013). Recently, global DNA methy- lation measured in peripheral blood has been investi- gated as a risk factor or a potential biologic mechanism for cancers of the breast, colorectum, stomach, or bladder in some epidemiologic studies (Terry et al., 2011; Barrow and Michels, 2014). However, data on how global DNA methylation in peripheral blood is related to the risk of lung cancer are still very limited (Zhu et al., 2011; Kitkumthorn et al., 2012). The present study explored the association between blood DNA methylation level and the risk of lung cancer in nonsmoking women from a multicenter study in Central and Eastern Europe. Materials and methods Study population Detailed study methods have been published previously (Lissowska et al., 2005). In brief, the study participants were recruited from a multicenter case–control study car- ried out in six Central and Eastern European countries during 1998–2001 (Lissowska et al., 2005). Cases were aged 20–75 years, diagnosed with primary, histologically, or cytologically confirmed incident lung cancer. Cases were enrolled in the study before treatment. In all centers, except Warsaw (Poland), controls were selected from Short paper 1 0959-8278 Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved. DOI: 10.1097/CEJ.0000000000000244 Copyright r 2016 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.