Open Access Open Badges Research article

Association of postmenopausal endogenous sex hormones with global methylation level of leukocyte DNA among Japanese women

Motoki Iwasaki1*, Hiroe Ono23, Aya Kuchiba24, Yoshio Kasuga5, Shiro Yokoyama6, Hiroshi Onuma6, Hideki Nishimura7, Ritsu Kusama8, Teruhiko Yoshida2 and Shoichiro Tsugane1

Author affiliations

1 Epidemiology and Prevention Division, Research Center for Cancer Prevention and Screening, National Cancer Center, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan

2 Division of Genetics, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan

3 Biomedical Science PhD Program, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan

4 Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Jimmy-Fund JF-605, Boston, MA, 02215, USA

5 Department of Surgery, Nagano Matsushiro General Hospital, 183 Matsushiro, Matsushiro-machi, Nagano-shi, Nagano, 381-1231, Japan

6 Department of Breast and Thyroid Surgery, Nagano Red Cross Hospital, 5-22-1 Wakasato, Nagano-shi, Nagano, 380-8582, Japan

7 Department of Surgery, Nagano Municipal Hospital, 1333-1 Tomitake, Nagano-shi, Nagano, 381-8551, Japan

8 Department of Surgery, Nagano Hokushin General Hospital, 1-5-63 Nishi, Nakano-shi, Nagano, 383-8505, Japan

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Citation and License

BMC Cancer 2012, 12:323  doi:10.1186/1471-2407-12-323

Published: 29 July 2012



Although global hypomethylation of leukocyte DNA has been associated with an increased risk of several sites of cancer, including breast cancer, determinants of global methylation level among healthy individuals remain largely unexplored. Here, we examined whether postmenopausal endogenous sex hormones were associated with the global methylation level of leukocyte DNA.


A cross-sectional study was conducted using the control group of a breast cancer case–control study in Nagano, Japan. Subjects were postmenopausal women aged 55 years or over who provided blood samples. We measured global methylation level of peripheral blood leukocyte DNA by luminometric methylation assay; estradiol, estrone, androstenedione, dehydroepiandrosterone sulfate, testosterone and free testosterone by radioimmunoassay; bioavailable estradiol by the ammonium sulfate precipitation method; and sex-hormone binding globulin by immunoradiometric assay. A linear trend of association between methylation and hormone levels was evaluated by regression coefficients in a multivariable liner regression model. A total of 185 women were included in the analyses.


Mean global methylation level (standard deviation) was 70.3% (3.1) and range was from 60.3% to 79.2%. Global methylation level decreased 0.27% per quartile category for estradiol and 0.39% per quartile category for estrone while it increased 0.41% per quartile category for bioavailable estradiol. However, we found no statistically significant association of any sex hormone level measured in the present study with global methylation level of leukocyte DNA.


Our findings suggest that endogenous sex hormones are not major determinants of the global methylation level of leukocyte DNA.

Cross-sectional study; Endogenous sex hormones; Global methylation level; Luminometric methylation assay; Peripheral blood leukocyte DNA