基于地点的结构性种族主义措施与乳腺癌死亡率存在关联，部分原因可能是通过表观遗传扰动来驱动。我们研究了当代红线划定，即衡量社区层面的结构性种族主义措施，与乳腺肿瘤组织中的DNA甲基化之间的关联。我们在艾默里大学医院（2008-2017年）诊断和治疗首次原发性乳腺癌的80名黑人和白人妇女中进行了研究。当代红线划定是使用住房按揭披露法案数据库为普查区划定的。线性回归模型用于计算当代红线划定和乳腺肿瘤组织中甲基化之间的关联。我们还研究了两种不同指标的表观遗传年龄加速度，将每个胞嘧啶-磷酸-鸟甘酸二核苷酸（CpG位点）的β值回归到红线划定上，并校正协变量。我们采用多变量Cox比例风险模型和95%置信区间（CI）来估计异常甲基化与死亡之间的关联。在多重比较校正后，当代红线划定与5个CpG位点相关联（FDR<0.10）。所有基因都与乳腺癌发生关联，包括与炎症、免疫功能和应激反应相关的基因（ANGPT1、PRG4和PRG4）。进一步研究前25个CpG位点发现，两个位点（MRPS28和cg11092048）与ER状态有交互作用，1个位点（GDP1）与全因死亡率相关。当代红线划定与Hannum衡量标准的表观遗传年龄加速度相关（β=5.35；CI 95%=0.30,10.4），并且与其他计时器呈正相关但未达到显著水平。我们发现了社区当代红线划定与乳腺肿瘤DNA甲基组之间的新型关联，表明导致不公平社会和环境暴露的种族主义政策可能会影响乳腺肿瘤表观遗传组。需要进一步研究其对预后的潜在影响。版权所有 © 2023 Miller-Kleinhenz, Moubadder, Beyer, Zhou, Gaglioti, Collin, Gohar, Do, Conneely, Krishnamurti, Gogineni, Gabram-Mendola, D’Angelo, Henry, Torres and McCullough.

Place-based measures of structural racism have been associated with breast cancer mortality, which may be driven, in part, by epigenetic perturbations. We examined the association between contemporary redlining, a measure of structural racism at the neighborhood level, and DNA methylation in breast tumor tissue.We identified 80 Black and White women diagnosed and treated for a first-primary breast cancer at Emory University Hospitals (2008-2017). Contemporary redlining was derived for census tracts using the Home Mortgage Disclosure Act database. Linear regression models were used to calculate the association between contemporary redlining and methylation in breast tumor tissue. We also examined epigenetic age acceleration for two different metrics, regressing β values for each cytosine-phosphate-guanine dinucleotide (CpG) site on redlining while adjusting for covariates. We employed multivariable Cox-proportional hazards models and 95% confidence intervals (CI) to estimate the association between aberrant methylation and mortality.Contemporary redlining was associated with 5 CpG sites after adjustment for multiple comparisons (FDR<0.10). All genes were implicated in breast carcinogenesis, including genes related to inflammation, immune function and stress response (ANGPT1, PRG4 and PRG4). Further exploration of the top 25 CpG sites, identified interaction of 2 sites (MRPS28 and cg11092048) by ER status and 1 site (GDP1) was associated with all-cause mortality. Contemporary redlining was associated with epigenetic age acceleration by the Hannum metric (β=5.35; CI 95%=0.30,10.4) and showed positive but non-significant correlation with the other clock.We identified novel associations between neighborhood contemporary redlining and the breast tumor DNA methylome, suggesting that racist policies leading to inequitable social and environmental exposures, may impact the breast tumor epigenome. Additional research on the potential implications for prognosis is needed.Copyright © 2023 Miller-Kleinhenz, Moubadder, Beyer, Zhou, Gaglioti, Collin, Gohar, Do, Conneely, Krishnamurti, Gogineni, Gabram-Mendola, D’Angelo, Henry, Torres and McCullough.