Association between serum organochlorines and global methylation level of leukocyte DNA among Japanese women: a cross-sectional study
Abstract
While the global methylation level of leukocyte DNA may be a suitable biomarker for cancer risk, the level may be influenced by multiple factors, both environmental and host-related, one of which is exposure to environmental pollutants. To date, three epidemiologic studies have examined associations between serum organochlorine levels and global DNA methylation level, but their findings are not fully consistent, and the associations thus require confirmation in other well-characterized populations. We tested the association between organochlorine exposure and the global DNA methylation level of leukocytes in Japanese women. We conducted a cross-sectional study using the control group of a breast cancer case-control study in Japan. Subjects were 403 Japanese women who provided blood samples. Serum polychlorinated biphenyls (PCBs) and nine pesticide-related organochlorines were measured by gas chromatography isotope-dilution high-resolution mass spectrometry. Further, global methylation level of peripheral leukocyte DNA among 399 women was measured by luminometric methylation assay. Linear trends in the association between methylation and quartile levels of organochlorines were evaluated by regression coefficients in a multivariable linear regression model. We found significant inverse associations between the global methylation level in leukocyte DNA and many of the organochlorine levels measured. Global methylation level was significantly decreased by 0.33-0.83% per quartile category for serum o,p'-dichlorodiphenyltrichloroethane (o,p'-DDT), p,p'-DDT, p,p'-dichlorodiphenyldichloroethylene, trans-nonachlor, oxychlordane, hexachlorobenzene, β-hexachlorocyclohexane, PCB17, PCB52/69, PCB74, PCB114, and PCB183. Serum organochlorine levels were inversely associated with the global methylation level of leukocyte DNA in a relatively large sample of Japanese women.
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DL and NDL PCBs have opposing actions on DNA methylation, with DL PCBs shifting the balance toward DNA hypermethylation and NDL PCBs favoring DNA hypomethylation.
“There is evidence to suggest that the DL and NDL PCBs have opposing actions on DNA methylation, with DL PCBs shifting the balance toward DNA hypermethylation, as was observed in the Sweden study [ 39 ], and NDL PCBs favoring DNA hypomethylation as observed in the Korean and Inuit studies [ 36 , 38 ].”
From DNA methylation: a mechanism linking environmental chemical exposures to risk of autism spectrum disorders? (2016) · cites this paper as [36]
In a cohort of 399 healthy Japanese women, serum levels of NDL PCBs 17, 52, 69, 74, 183, and DL PCB 114 were inversely associated with global DNA methylation levels in leukocytes.
“In a cohort of 399 healthy Japanese women, serum levels of NDL PCBs 17, 52, 69, 74, 183, and DL PCB 114 were inversely associated with global DNA methylation levels in leukocytes [ 36 ].”
From DNA methylation: a mechanism linking environmental chemical exposures to risk of autism spectrum disorders? (2016) · cites this paper as [36]
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- Authors
- Itoh, H., Iwasaki, M., Kasuga, Y., Yokoyama, S., Onuma, H., Nishimura, H., Kusama, R., Yoshida, T., Yokoyama, K., & Tsugane, S.
- Affiliations
- Juntendo University (JP)
- National Cancer Centre Japan (JP)
- Nagano Matsushiro General Hospital (JP)
- Nagano Red Cross Hospital (JP)
- Nagano Municipal Hospital (JP)
- Hokushin General Hospital (JP)
- National Cancer Center Research Institute (JP)
- Corresponding author
- Iwasaki, Motoki
- Venue
- Science of The Total Environment
- Publisher
- Elsevier BV
- Published
- 2014-08
- Volume
- 490
- Pages
- 603-609
- ISSN
- 0048-9697 (ISSN-L)
- OpenAlex
- W1983262171
- Cited by
- 53
- References
- 23
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 3 · 2023: 2 · 2022: 5 · 2021: 7 · 2020: 1 · 2019: 8 · 2018: 6 · 2017: 12 · 2016: 5 · 2015: 2
- FWCI
- 2.60
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Science of The Total Environment (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Foundation for Promotion of Cancer Research
- Japan Society for the Promotion of Science
- National Institute of Biomedical Innovation (221S0001, 22700934)
- Ministry of Education, Culture, Sports, Science and Technology
- Ministry of Health, Labour and Welfare
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Pesticide Exposure and Toxicity
- Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Toxic Organic Pollutants Impact
- Keywords
- organochlorine compounds, global DNA methylation, leukocyte DNA, polychlorinated biphenyls, pesticide exposure, DDT, environmental pollutants, epigenetics, cancer risk biomarkers, Japanese women
- MeSH terms
- Adult, Cross-Sectional Studies, Environmental Exposure, Environmental Pollutants, Environmental Pollution, Female, Humans, Hydrocarbons, Chlorinated, Japan, Leukocytes, Middle Aged, Epidemiologic Studies, DNA Methylation
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