Association between serum concentrations of perfluoroalkyl substances and global DNA methylation levels in peripheral blood leukocytes of Japanese women: A cross-sectional study
Association between serum concentrations of perfluoroalkyl substances and global DNA methylation levels in peripheral blood leukocytes of Japanese women: A cross-sectional study
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DOI：
10.1016/j.scitotenv.2022.159923
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发表时间：
2022-11-17
影响因子：
9.8
通讯作者：
Iwasaki, Motoki
中科院分区：
文献类型：
--
作者：
Itoh, Hiroaki;Harada, Kouji H.;Iwasaki, Motoki
外周血白细胞中的整体DNA甲基化水平可以是癌症风险的生物标志物;然而，水平可以通过各种因素（如环境污染物）改变。我们在日本乳腺癌病例对照研究[397名平均年龄为54.1（SD 10.1）岁的女性]的对照组中进行了一项横断面研究，调查了血清全氟烷基物质（PFAS）浓度与白细胞总体DNA甲基化水平之间的关系。重要的是，我们的分析区分支化PFAS异构体不同于线性异构体。采用端口芳化气相色谱负化学电离质谱法测定了20种PFAS的血清浓度。使用发光甲基化测定法测量外周血白细胞中的总体DNA甲基化水平。通过多变量稳健线性回归分析中的回归系数评估log 10转换的血清PFAS浓度与总体DNA甲基化水平之间的关联。13种PFAS血清浓度与白细胞DNA甲基化水平显著相关。血清PFAS浓度每增加1个log 10单位，总DNA甲基化显著增加1.45%-3.96%.我们的研究结果表明，暴露于PFASs可能会增加日本妇女外周血白细胞的整体DNA甲基化水平。
Global DNA methylation levels in peripheral blood leukocytes can be a biomarker for cancer risk; however, levels can be changed by various factors such as environmental pollutants. We investigated the association between serum con-centrations of perfluoroalkyl substances (PFASs) and global DNA methylation levels of leukocytes in a cross-sectional study using the control group of a Japanese breast cancer case-control study [397 women with a mean age of 54.1 (SD 10.1) years]. Importantly, our analysis distinguished branched PFAS isomers as different from linear isomers. The serum concentrations of 20 PFASs were measured by in-port arylation gas-chromatography negative chemical ioniza-tion mass spectrometry. Global DNA methylation levels in peripheral blood leukocytes were measured using a luminometric methylation assay. Associations between log10-transformed serum PFAS concentrations and global DNA methylation levels were evaluated by regression coefficients in multivariable robust linear regression analyses. Serum concentrations of 13 PFASs were significantly associated with increased global DNA methylation levels in leu-kocytes. Global DNA methylation was significantly increased by 1.45 %-3.96 % per log10-unit increase of serum PFAS concentration. Our results indicate that exposure to PFASs may increase global DNA methylation levels in peripheral blood leukocytes of Japanese women.