Global DNA hypomethylation in leukocytes associated with glioma risk

Abstract

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.

Evidence for age‐related contributions of DNA damage and epigenetics in brain tumorigenesis

“…Lower levels of methylation seen in glioblastoma samples were weighted into the younger group with increasing methylation levels with advancing age (Figure A). A global hypomethylated state associated with glioma risk was observed in a previous study in leucocytes 32 . Although regression analysis of increased genomic methylation levels with increasing age did not reach significance by regression analysis, the trend is consistent with hypomethylation in the younger age group, These data provide further evidence regarding the role of genomic hypomethylation in glioblastoma, especially in young patients.…”

Caffeic acid and chlorogenic acid cytotoxicity, genotoxicity and impact on global DNA methylation in human leukemic cell lines

“…Analysis of global DNA methylation revealed that non-treated HL-60 and Jurkat cells exhibited 2.3% and 2.9% of 5-mC DNA, respectively. The 5-mC levels in primary human fibroblasts ranged from 1.0% to 1.7% ( Maierhofer et al , 2017 ), while the mean 5-mC level was 2.8% in peripheral blood of 100 male workers employed in automotive battery factories ( Devoz et al , 2017 ), 3.82% in leukocytes from 390 volunteers with no known cancer ( Shen et al. , 2017 ), and 2.28% in non-treated LNCaP human prostate cancer cells in vitro ( Wu et al , 2017 ).…”

Leukocyte telomere length associated with glioma risk and survival

“…Detailed recruitment method for glioma patients and healthy controls was reported in our previous publication 34 . In brief, a total of 565 glioma patients and 1130 healthy controls were included in the study.…”

“…Detailed recruitment method for glioma patients and healthy controls was reported in our previous publication. 34 In brief, a total of 565 glioma patients and 1130 healthy controls were included in the study. The cases were newly diagnosed histologically confirmed glioma patients seen at The University of Texas M. D. Anderson Cancer Center (MDACC) between April 2014 and July 2018.…”