Association of postmenopausal endogenous sex hormones with global methylation level of leukocyte DNA among Japanese women
Association of postmenopausal endogenous sex hormones with global methylation level of leukocyte DNA among Japanese women
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DOI：
10.1186/1471-2407-12-323
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发表时间：
2012-07-29
期刊：
影响因子：
3.8
通讯作者：
Tsugane, Shoichiro
中科院分区：
文献类型：
--
作者：
Iwasaki, Motoki;Ono, Hiroe;Tsugane, Shoichiro
背景资料：尽管白细胞DNA的整体低甲基化与包括乳腺癌在内的几个癌症部位的风险增加有关，但健康个体中整体甲基化水平的决定因素在很大程度上仍未被探索。在这里，我们研究是否绝经后内源性性激素与全球甲基化水平的白细胞DNA.Methods：一个横断面研究进行了使用的乳腺癌病例对照研究在长野，日本的对照组。受试者为年龄55岁或以上的绝经后女性，提供血液样本。我们测量了全球甲基化水平的外周血白细胞DNA的发光甲基化分析;雌二醇，雌酮，雄烯二酮，硫酸脱氢表雄酮，睾酮和游离睾酮的放射免疫分析;生物可利用的雌二醇的硫酸铵沉淀法;和性激素结合球蛋白的免疫放射分析。通过多变量线性回归模型中的回归系数评估甲基化和激素水平之间的相关性的线性趋势。结果：平均整体甲基化水平（标准差）为70.3%（3.1），范围为60.3%至79.2%。总甲基化水平下降0.27%，每四分位数类雌二醇和0.39%，每四分位数类雌酮，而它增加了0.41%，每四分位数类生物可利用的雌二醇。然而，我们没有发现任何性激素水平在本研究中测量与全球甲基化水平的白细胞DNA.Conclusions：我们的研究结果表明，内源性性激素不是全球甲基化水平的主要决定因素白细胞DNA。
Background: 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.Methods: 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.Results: 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.Conclusions: Our findings suggest that endogenous sex hormones are not major determinants of the global methylation level of leukocyte DNA.