Abstract
BackgroundChronic inflammatory conditions are associated with higher tumor incidence through epigenetic and genetic alterations. Here, we focused on an association between an inflammation marker, C-reactive-protein (CRP), and global DNA methylation levels of peripheral blood leukocytes.MethodsThe subjects were 384 healthy Japanese women enrolled as the control group of a case-control study for breast cancer conducted from 2001 to 2005. Global DNA methylation was quantified by Luminometric Methylation Assay (LUMA).ResultsWith adjustment for lifestyle-related factors, including folate intake, the global DNA methylation level of peripheral blood leukocytes was significantly but weakly increased by 0.43% per quartile category for CRP (P for trend = 0.010). Estimated methylation levels stratified by CRP quartile were 70.0%, 70.8%, 71.4%, and 71.3%, respectively. In addition, interaction between polymorphism of MTHFR (rs1801133, known as C677T) and CRP was significant (P for interaction = 0.046); the global methylation level was significantly increased by 0.61% per quartile category for CRP in the CT/TT group (those with the minor allele T, P for trend = 0.001), whereas no association was observed in the CC group (wild type).ConclusionsOur study suggests that CRP concentration is weakly associated with global DNA methylation level. However, this association was observed more clearly in individuals with the minor allele of the MTHFR missense SNP rs1801133. By elucidating the complex mechanism of the regulation of DNA methylation by both acquired and genetic factors, our results may be important for cancer prevention.
Highlights
Chronic inflammatory conditions are associated with higher tumor incidence through epigenetic and genetic alterations
Several studies have reported an association between the level of global methylation of the peripheral blood leukocytes and the development of cancers, which suggests that metabolic conditions in cancer patients may induce aberrant DNA methylation systemically, in the primary organ [4,5,6,7]
Higher tumor incidence is associated with various chronic inflammatory conditions, such as H. pylori (HP) gastritis and ulcerative colitis (UC), and previous reports suggest that the mechanisms of these associations can be through epigenetic alterations [8, 13]
Summary
Chronic inflammatory conditions are associated with higher tumor incidence through epigenetic and genetic alterations. We focused on an association between an inflammation marker, C-reactive-protein (CRP), and global DNA methylation levels of peripheral blood leukocytes. Several studies have reported an association between the level of global methylation of the peripheral blood leukocytes and the development of cancers, which suggests that metabolic conditions in cancer patients may induce aberrant DNA methylation systemically, in the primary organ [4,5,6,7]. Higher tumor incidence is associated with various chronic inflammatory conditions, such as H. pylori (HP) gastritis and ulcerative colitis (UC), and previous reports suggest that the mechanisms of these associations can be through epigenetic alterations [8, 13]. In a colitis-induced mouse model, DNA hypermethylation was induced in low CpG regions called “DNA methylation valleys” [14]
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