The Effects of Lifetime Estrogen Exposure on Breast Epigenetic Age.
The Effects of Lifetime Estrogen Exposure on Breast Epigenetic Age.
复制标题
终生雌激素暴露对乳腺表观遗传时代的影响。
DOI：
10.1158/1055-9965.epi-20-1297
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发表时间：
2021-06
期刊：
影响因子：
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通讯作者：
Ganz PA
中科院分区：
文献类型：
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作者：
Sehl ME;Henry JE;Storniolo AM;Horvath S;Ganz PA
雌激素被认为是通过细胞周期和加速乳房衰老来增加乳腺癌的风险。我们假设，一生雌激素暴露驱动早期表观遗传乳腺衰老观察健康女性。在这项研究中，我们研究了健康乳腺组织中激素因素和表观遗传衰老措施之间的关联。我们从192名健康女性捐献者的乳腺组织标本中提取DNA。印第安纳州西蒙大学癌症中心的科门组织库。使用Illumina EPIC 850 K阵列平台进行甲基化实验。使用经方差调整的回归模型来检查与雌激素暴露相关的因素与五种基于DNA甲基化的估计值之间的关联：格里姆年龄、泛组织年龄、汉南年龄、表型年龄以及皮肤和血液时钟年龄。女性年龄为19-90岁，其中95名为绝经前女性，97名为未经产女性。接近初潮的年龄越早，年龄差异（年龄-年龄）越大。我们发现，根据格里姆时钟、皮肤和血液时钟，初潮年龄较早与年龄调整后的加速度之间存在显着关联，较高的体重指数（BMI）与格里姆时钟、汉纳姆时钟、表型时钟和皮肤和血液时钟中的年龄调整后的加速度之间存在显着关联。初潮年龄较早和BMI较高与健康乳腺组织中基于DNA甲基化的年龄估计值升高相关，这表明累积的雌激素暴露会驱动乳腺表观遗传衰老。表观遗传时钟措施可能有助于推进调查加速乳腺组织衰老和年轻女性乳腺癌发病率升高之间的关系。
Estrogens are thought to contribute to breast cancer risk through cell cycling and accelerated breast aging. We hypothesize that lifetime estrogen exposure drives early epigenetic breast aging observed in healthy women. In this study, we examined associations between hormonal factors and epigenetic aging measures in healthy breast tissues. We extracted DNA from breast tissue specimens from 192 healthy female donors to the Susan G. Komen Tissue Bank at the Indiana University Simon Cancer Center. Methylation experiments were performed using the Illumina EPIC 850K array platform. Age-adjusted regression models were used to examine for associations between factors related to estrogen exposure and five DNA methylation-based estimates: Grim age, Pan-tissue age, Hannum age, Phenotypic age, and Skin and Blood Clock age. Women were aged 19–90 years, with 95 pre-menopausal, and 97 nulliparous women. The age difference (Grim age - chronologic age) was higher at earlier ages close to menarche. We found significant associations between earlier age at menarche and age-adjusted accelerations according to the Grim clock, the Skin and Blood clock, and between higher body mass index (BMI) and age-adjusted accelerations in the Grim clock, Hannum clock, Phenotypic clock, and Skin and Blood clock. Earlier age at menarche and higher BMI are associated with elevations in DNA methylation-based age estimates in healthy breast tissues, suggesting that cumulative estrogen exposure drives breast epigenetic aging. Epigenetic clock measures may help advance inquiry into the relationship between accelerated breast tissue aging and an elevated incidence of breast cancer in younger women.