乳腺肿瘤中的邻域剥夺和 DNA 甲基化以及癌症基因的表达。
Neighborhood Deprivation and DNA Methylation and Expression of Cancer Genes in Breast Tumors.
发表日期:2023 Nov 01
作者:
Brittany D Jenkins, Emily Rossi, Catherine Pichardo, William Wooten, Margaret Pichardo, Wei Tang, Tiffany H Dorsey, Anuoluwapo Ajao, Ruby Hutchison, Leah Moubadder, Lauren E McCullough, Maeve Bailey-Whyte, Stefan Ambs
来源:
JAMA Network Open
摘要:
邻里环境与癌症等慢性疾病之间关系的生物过程仍然知之甚少。为了确定乳腺组织 DNA 甲基化的差异是否与患有乳腺癌的黑人和白人妇女的邻里剥夺有关。这项横断面研究收集了 1993 年 1 月 1 日至 2003 年 12 月 31 日期间接受乳腺癌手术的妇女的乳腺组织。参与者是通过马里兰大学医学中心招募的,在巴尔的摩地区的医院也有其他收集点。数据分析于 2022 年 3 月 1 日至 12 月 1 日进行。2000 年人口普查区域层面的社会经济剥夺通过邻里剥夺指数 (NDI) 作为标准化分数来衡量,黑人和白人种族通过自我报告确定。主要结果是使用全基因组测量的组织 DNA 甲基化。次要结果是组织基因表达。参与者包括 185 名患有乳腺癌的女性(110 名黑人 [59.5%],75 名白人 [40.5%])。手术时平均 (SD) 年龄为 56.0 (14.1) 岁。黑人女性的邻里剥夺程度高于白人女性(平均 [SD] NDI,黑人女性为 2.96 [3.03],白人女性为 -0.54 [1.91];差值,-3.50;95% CI,-4.22 至 -2.79; P < .001)。在非分层分析中,8 个低甲基化 CpG 位点被鉴定为与 NDI 相关,包括 2 个肿瘤抑制基因 LRIG1 和 WWOX 中的位点。此外,这两个基因的表达与邻里剥夺呈负相关。在种族分层分析中,黑人女性中 LRIG1 基因体 CpG 位点 cg26131019 与 NDI 之间的负相关性仍然显着。在黑人女性肿瘤中,还观察到 LRIG1 和 WWOX 的基因表达与邻域剥夺相关。在这项研究中,高邻域剥夺与黑人女性组织 DNA 甲基化和基因表达的差异相关。这些发现表明,对社区一级的公共卫生干预措施和政策变化的持续投资可能有助于纠正可能使少数群体更容易患慢性病的生物改变。
The biological processes that underlie the association of neighborhood environment with chronic diseases, such as cancer, remain poorly understood.To determine whether differences in breast tissue DNA methylation are associated with neighborhood deprivation among Black and White women with breast cancer.This cross-sectional study collected breast tissue from women undergoing surgery for breast cancer between January 1, 1993, and December 31, 2003. Participants were recruited through the University of Maryland Medical Center, with additional collection sites at Baltimore-area hospitals. Data analysis was performed from March 1 through December 1, 2022.Year 2000 census tract-level socioeconomic deprivation measured via neighborhood deprivation index (NDI) as a standardized score, with Black and White race being ascertained through self-report.The primary outcome was tissue DNA methylation using genome-wide measurements. The secondary outcome was tissue gene expression.Participants included 185 women with breast cancer (110 Black [59.5%], 75 White [40.5%]). Mean (SD) age at surgery was 56.0 (14.1) years. Neighborhood deprivation was higher for Black women than for White women (Mean [SD] NDI, 2.96 [3.03] for Black women and -0.54 [1.91] for White women; difference, -3.50; 95% CI, -4.22 to -2.79; P < .001). In unstratified analysis, 8 hypomethylated CpG sites were identified as associated with the NDI, including sites in 2 tumor suppressor genes, LRIG1 and WWOX. Moreover, expression of the 2 genes inversely correlated with neighborhood deprivation. In the race-stratified analysis, the negative correlation between the LRIG1 gene body CpG site cg26131019 and the NDI remained significant in Black women. A neighborhood deprivation-associated decrease in gene expression was also observed for LRIG1 and WWOX in tumors from Black women.In this study, high neighborhood deprivation was associated with differences in tissue DNA methylation and gene expression among Black women. These findings suggest that continued investment in public health interventions and policy changes at the neighborhood level may help to remedy biological alterations that could make minoritized populations more susceptible to chronic diseases.