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Sci Total Environ. 2014 Aug 15;490:603-9. doi: 10.1016/j.scitotenv.2014.05.035. Epub 2014 Jun 2.

Association between serum organochlorines and global methylation level of leukocyte DNA among Japanese women: a cross-sectional study.

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Department of Epidemiology and Environmental Health, Juntendo University Faculty of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421 Japan.
Epidemiology Division, Research Center for Cancer Prevention and Screening, National Cancer Center, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045 Japan. Electronic address:
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.
Dierctor Research Center for Cancer Prevention and Screening, National Cancer Center, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045 Japan.


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.


DNA methylation; Persistent organic pollutants; epidemiology; epigenetics; polychlorinated biphenyl

[Indexed for MEDLINE]

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