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首页> 外文期刊>Epigenetics: official journal of the DNA Methylation Society >Global DNA methylation levels in white blood cell DNA from sisters discordant for breast cancer from the New York site of the breast cancer family registry
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Global DNA methylation levels in white blood cell DNA from sisters discordant for breast cancer from the New York site of the breast cancer family registry

机译：来自乳腺癌家庭登记处纽约站点的姐妹患乳腺癌的白细胞DNA中的全球DNA甲基化水平

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Lower global DNA methylation is associated with genomic instability and it is one of the epigenetic mechanisms relevant to carcinogenesis. Emerging evidence for several cancers suggests that lower overall levels of global DNA methylation in blood are associated with different cancer types, although less is known about breast cancer. We examined global DNA methylation levels using a sibling design in 273 sisters affected with breast cancer and 335 unaffected sisters from the New York site of the Breast Cancer Family Registry. We measured global DNA methylation in total white blood cell (WBC) and granulocyte DNA by two different methods, the [3H]-methyl acceptance assay and the luminometric methylation assay (LUMA). Global methylation levels were only modestly correlated between sisters discordant for breast cancer (Spearman correlation coefficients ranged from -0.08 to 0.24 depending on assay and DNA source). Using conditional logistic regression models, women in the quartile with the lowest DNA methylation levels (as measured by the [3H]-methyl acceptance assay) had a 1.8-fold (95% CI = 1.0-3.3) higher relative association with breast cancer than women in the quartile with the highest DNA methylation levels. When we examined the association on a continuous scale, we also observed a positive association (odds ratio, OR = 1.3, 95% CI = 1.0-1.7, for a one unit change in the natural logarithm of the DPM/μg of DNA). We observed no association between measures by the LUMA assay and breast cancer risk. If replicated in prospective studies, this study suggests that global DNA methylation levels measured in WBC may be a potential biomarker of breast cancer risk even within families at higher risk of cancer.
机译：较低的整体DNA甲基化与基因组不稳定有关，并且是与致癌作用有关的表观遗传机制之一。几种癌症的新证据表明，血液中总体DNA甲基化水平的降低与不同类型的癌症有关，尽管对乳腺癌的了解较少。我们使用同级设计研究了乳腺癌家庭登记处纽约站点的273名患乳腺癌的姐妹和335名未受影响的姐妹的总体DNA甲基化水平。我们通过两种不同的方法[3H]-甲基接受测定和发光甲基化测定（LUMA）测量了总白细胞（WBC）和粒细胞DNA中的总体DNA甲基化。乳腺癌患者之间姐妹之间的总体甲基化水平仅适度相关（Spearman相关系数的范围从-0.08到0.24，具体取决于测定方法和DNA来源）。使用条件逻辑回归模型，四分位数中具有最低DNA甲基化水平（通过[3H]-甲基接受分析测定）的女性与乳腺癌的相对关联性比女性高1.8倍（95％CI = 1.0-3.3）四分位数中女性的DNA甲基化水平最高。当我们以连续规模检查关联时，我们还观察到了正关联（DPM /μgDNA的自然对数变化一个单位时，优势比，OR = 1.3，95％CI = 1.0-1.7）。我们观察到通过LUMA分析的方法与乳腺癌风险之间没有关联。如果在前瞻性研究中重复使用，则该研究表明，即使在癌症风险较高的家庭中，在WBC中测得的全球DNA甲基化水平也可能是潜在的乳腺癌风险生物标志物。

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