title: 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.affiliation: Department of Epidemiology and Environmental Health, Juntendo University Faculty of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421 Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Itoh
authors.affiliation: Epidemiology Division, Research Center for Cancer Prevention and Screening, National Cancer Center, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045 Japan. Electronic address: moiwasak@ncc.go.jp.
authors.forename: Motoki
authors.initials: M
authors.lastname: Iwasaki
authors.affiliation: Department of Surgery, Nagano Matsushiro General Hospital, 183 Matsushiro, Matsushiro-cho, Nagano City, Nagano Prefecture 381-1231 Japan.
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Kasuga
authors.affiliation: Department of Breast and Thyroid Surgery, Nagano Red Cross Hospital, 5-22-1 Wakasato, Nagano City, Nagano Prefecture 380-8582 Japan.
authors.forename: Shiro
authors.initials: S
authors.lastname: Yokoyama
authors.affiliation: Department of Breast and Thyroid Surgery, Nagano Red Cross Hospital, 5-22-1 Wakasato, Nagano City, Nagano Prefecture 380-8582 Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Onuma
authors.affiliation: Department of Respiratory Surgery and Breast Surgery, Nagano Municipal Hospital, 1333-1 Tomitake, Nagano City, Nagano Prefecture 381-8551 Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Nishimura
authors.affiliation: Department of Surgery, Hokushin General Hospital, 1-5-63 Nishi, Nakano City, Nagano Prefecture 383-8505 Japan.
authors.forename: Ritsu
authors.initials: R
authors.lastname: Kusama
authors.affiliation: Division of Genetics, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045 Japan.
authors.forename: Teruhiko
authors.initials: T
authors.lastname: Yoshida
authors.affiliation: Department of Epidemiology and Environmental Health, Juntendo University Faculty of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421 Japan.
authors.forename: Kazuhito
authors.initials: K
authors.lastname: Yokoyama
authors.affiliation: Dierctor Research Center for Cancer Prevention and Screening, National Cancer Center, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045 Japan.
authors.forename: Shoichiro
authors.initials: S
authors.lastname: Tsugane
mesh_terms: D000328:Adult; D003430:Cross-Sectional Studies; D019175:DNA Methylation; D004781:Environmental Exposure / Q000032:analysis* / Q000706:statistics & numerical data; D004785:Environmental Pollutants / Q000378:metabolism* / Q000633:toxicity; D004787:Environmental Pollution / Q000706:statistics & numerical data*; D016021:Epidemiologic Studies; D005260:Female; D006801:Humans; D006843:Hydrocarbons, Chlorinated / Q000378:metabolism* / Q000633:toxicity; D007564:Japan; D007962:Leukocytes / Q000187:drug effects* / Q000502:physiology; D008875:Middle Aged
chemical_list: D004785:Environmental Pollutants; D006843:Hydrocarbons, Chlorinated
keywords: DNA methylation; Persistent organic pollutants; epidemiology; epigenetics; polychlorinated biphenyl