Abstract
BackgroundGood biomarkers for early detection of cancer lead to better prognosis. However, harvesting tumor tissue is invasive and cannot be routinely performed. Global DNA methylation of peripheral blood leukocyte DNA was evaluated as a biomarker for cancer risk.MethodsWe performed a meta-analysis to estimate overall cancer risk according to global DNA hypomethylation levels among studies with various cancer types and analytical methods used to measure DNA methylation. Studies were systemically searched via PubMed with no language limitation up to July 2011. Summary estimates were calculated using a fixed effects model.ResultsThe subgroup analyses by experimental methods to determine DNA methylation level were performed due to heterogeneity within the selected studies (p<0.001, I2: 80%). Heterogeneity was not found in the subgroup of %5-mC (p = 0.393, I2: 0%) and LINE-1 used same target sequence (p = 0.097, I2: 49%), whereas considerable variance remained in LINE-1 (p<0.001, I2: 80%) and bladder cancer studies (p = 0.016, I2: 76%). These results suggest that experimental methods used to quantify global DNA methylation levels are important factors in the association study between hypomethylation levels and cancer risk. Overall, cancer risks of the group with the lowest DNA methylation levels were significantly higher compared to the group with the highest methylation levels [OR (95% CI): 1.48 (1.28–1.70)].ConclusionsGlobal DNA hypomethylation in peripheral blood leukocytes may be a suitable biomarker for cancer risk. However, the association between global DNA methylation and cancer risk may be different based on experimental methods, and region of DNA targeted for measuring global hypomethylation levels as well as the cancer type. Therefore, it is important to select a precise and accurate surrogate marker for global DNA methylation levels in the association studies between global DNA methylation levels in peripheral leukocyte and cancer risk.
Highlights
Epigenetic processes are important in development and cell differentiation, and can be altered by environment, diet, and aging [1,2]
Woloszynska-Read et al [25] has suggested that the ratio of Brother of the regulator of imprinted sites (BORIS)/CCCTC-binding factor (CTCF) expression is related to DNA demethylation
The inclusion/ exclusion criteria were as follows: (1) the original article with casecontrol or cohort designs; (2) peripheral blood leukocytes were used to measure global DNA methylation levels; (3) patients who were newly diagnosed with cancer in case-control studies, and blood was collected in participants who were free of cancers at baseline in cohort studies; (4) the studies with gene-specific DNA methylation were excluded; and (5) the study reported 95% confidence intervals (CI) with adjusted odds ratios (OR) or relative risks (RR) for cancer risk in subjects with the lowest level of global DNA methylation compared to that in patients with the highest level of global DNA methylation
Summary
Epigenetic processes are important in development and cell differentiation, and can be altered by environment, diet, and aging [1,2]. DNA methylation, which is a major epigenetic mechanism, is involved in various biological processes including cancer [3,4,5,6]. DNA hypomethylation is an early event in human carcinogenesis [7,8,9] and is associated with genetic instability in cancer cells [10,11]. Woloszynska-Read et al [25] has suggested that the ratio of BORIS/CCCTC-binding factor (CTCF) expression is related to DNA demethylation. Because direct removal of the methyl group from the 59 position of the cytosine is unfavorable, studies suggesting natural mechanisms of DNA demethylation have been inconsistent. Global DNA methylation of peripheral blood leukocyte DNA was evaluated as a biomarker for cancer risk
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