Research Papers:

Global DNA hypomethylation in leukocytes associated with glioma risk

Jie Shen, Renduo Song, Ye Gong and Hua Zhao _

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Oncotarget. 2017; 8:63223-63231. https://doi.org/10.18632/oncotarget.18739

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Jie Shen1, Renduo Song1, Ye Gong2 and Hua Zhao1

1Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

2Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China

Correspondence to:

Hua Zhao, email: [email protected]

Keywords: glioma, global DNA hypomethylation, leukocytes, cancer risk

Abbreviations: isocitrate dehydrogenase (IDH), body mass index (BMI)

Received: April 21, 2017     Accepted: May 21, 2017     Published: June 28, 2017


Global DNA hypomethylation in leukocytes has been associated with increased risk for a variety of cancers. However, the role of leukocyte global DNA hypomethylation in glioma development, if any, is largely unknown. To define this role, we performed a case-control study with 390 glioma patients and 390 controls with no known cancer. Levels of 5-methylcytosine (5-mC%), a marker for global DNA methylation, were measured in leukocyte DNA. Overall, median levels of 5-mC% were significantly lower in glioma cases than in controls (3.45 vs 3.82, P=0.001). Levels of 5-mC% differed significantly by age and sex among controls and by tumor subtype and grade among glioma cases. In multivariate analysis, lower levels of 5-mC% were associated with a 1.31-fold increased risk of glioma (odds ratio = 1.31, 95% confidence interval = 1.10-1.41). A significant dose-response trend was observed in quartile analysis (P=0.001). In an analysis further stratified by clinical characteristics at baseline, the association between lower levels of 5-mC% and glioma risk was evident only among younger participants (age <52 years), women, and those with aggressive tumor characteristics, such as glioblastoma subtype, high tumor grade (grade III or IV), and absence of IDH1 mutation. Our findings indicate that global DNA hypomethylation in leukocytes may contribute to the development of glioma and that the association is affected by age, sex, and tumor aggressiveness.

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