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.

• Authors: Hiroaki Itoh, Motoki Iwasaki, Yoshio Kasuga, Shiro Yokoyama, Hiroshi Onuma, Hideki Nishimura, Ritsu Kusama, Teruhiko Yoshida, Kazuhito Yokoyama, Shoichiro Tsugane
• Journal: The Science of the total environment (Sci Total Environ) Vol. 490 Pg. 603-9 (Aug 15 2014) ISSN: 1879-1026 [Electronic] Netherlands
• PMID: 24880549 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier B.V. All rights reserved.

Chemical References

• Environmental Pollutants
• Hydrocarbons, Chlorinated

Topics

• Adult
• Cross-Sectional Studies
• DNA Methylation
• Environmental Exposure (analysis, statistics & numerical data)
• Environmental Pollutants (metabolism, toxicity)
• Environmental Pollution (statistics & numerical data)
• Epidemiologic Studies
• Female
• Humans
• Hydrocarbons, Chlorinated (metabolism, toxicity)
• Japan
• Leukocytes (drug effects, physiology)
• Middle Aged