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BMC Cancer. 2018 Feb 13;18(1):184. doi: 10.1186/s12885-018-4089-z.

Correlation between global methylation level of peripheral blood leukocytes and serum C reactive protein level modified by MTHFR polymorphism: a cross-sectional study.

Author information

Center for Translational Research, The Institute of Medical Science Hospital, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo, 108-8639, Japan.
Division of Epidemiology, Research Center for Cancer Prevention and Screening, National Cancer Center, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan.
Department of Surgery, Nagano Matsushiro General Hospital, 183 Matsushiro, Matsushiro-cho, Nagano City, Nagano Prefecture, 381-1231, Japan.
Department of Breast and Thyroid Surgery, Nagano Red Cross Hospital, 5-22-1 Wakasato, Nagano City, Nagano Prefecture, 380-8582, Japan.
Department of Respiratory Surgery and Breast Surgery, Nagano Municipal Hospital, 1333-1 Tomitake, Nagano City, Nagano Prefecture, 381-8551, Japan.
Department of Surgery, Hokushin General Hospital, 1-5-63 Nishi, Nakano City, Nagano Prefecture, 383-8505, Japan.
Division of Genetics, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan.
Research Center for Cancer Prevention and Screening, National Cancer Center, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan.



Chronic 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.


The 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).


With 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).


Our 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.


C reactive protein; DNA methylation; Folate intake; Folate metabolism; Inflammation

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