Department of Biostatistics, Virginia Commonwealth University, Richmond.
Massey Comprehensive Cancer Center, Richmond, Virginia.
JAMA Netw Open. 2024 Jul 1;7(7):e2421903. doi: 10.1001/jamanetworkopen.2024.21903.
African American men experience greater prostate cancer incidence and mortality than White men. Growing literature supports associations of neighborhood disadvantage, which disproportionately affects African American men, with aggressive prostate cancer; chronic stress and downstream biological impacts (eg, increased inflammation) may contribute to these associations.
To examine whether several neighborhood disadvantage metrics are associated with prostate tumor RNA expression of stress-related genes.
DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study leveraged prostate tumor transcriptomic data for African American and White men with prostate cancer who received radical prostatectomy at the University of Maryland Medical Center between August 1992 and January 2021. Data were analyzed from May 2023 to April 2024.
Using addresses at diagnosis, 2 neighborhood deprivation metrics (Area Deprivation Index [ADI] and validated bayesian Neighborhood Deprivation Index) as well as the Racial Isolation Index (RI) and historical redlining were applied to participants' addresses. Self-reported race was determined using electronic medical records.
A total of 105 stress-related genes were evaluated with each neighborhood metric using linear regression, adjusting for race, age, and year of surgery. Genes in the Conserved Transcriptional Response to Adversity (CTRA) and stress-related signaling genes were included.
A total of 218 men (168 [77%] African American, 50 [23%] White) with a median (IQR) age of 58 (53-63) years were included. African American participants experienced greater neighborhood disadvantage than White participants (median [IQR] ADI, 115 [100-130] vs 92 [83-104]; median [IQR] RI, 0.68 [0.34-0.87] vs 0.11 [0.06-0.14]). ADI was positively associated with expression for 11 genes; HTR6 (serotonin pathway) remained significant after multiple-comparison adjustment (β = 0.003; SE, 0.001; P < .001; Benjamini-Hochberg q value = .01). Several genes, including HTR6, were associated with multiple metrics. We observed higher expression of 5 proinflammatory genes in the CTRA with greater neighborhood disadvantage (eg, CXCL8 and ADI, β = 0.008; SE, 0.003; P = .01; q value = .21).
In this cross-sectional study, the expression of several stress-related genes in prostate tumors was higher among men residing in disadvantaged neighborhoods. This study is one of the first to suggest associations of neighborhood disadvantage with prostate tumor RNA expression. Additional research is needed in larger studies to replicate findings and further investigate interrelationships of neighborhood factors, tumor biology, and aggressive prostate cancer to inform interventions to reduce disparities.
非裔美国男性患前列腺癌的发病率和死亡率高于白种男性。越来越多的文献支持邻里贫困（这对非裔美国男性的影响不成比例）与侵袭性前列腺癌之间存在关联；慢性压力和下游生物学影响（例如，炎症增加）可能促成这些关联。
研究几种邻里劣势指标是否与非裔美国人和白人前列腺癌患者的前列腺肿瘤 RNA 表达中的应激相关基因有关。
设计、地点和参与者：这项横断面研究利用了马里兰大学医学中心于 1992 年 8 月至 2021 年 1 月期间接受根治性前列腺切除术的患有前列腺癌的非裔美国男性和白种男性的前列腺肿瘤转录组数据。数据于 2023 年 5 月至 2024 年 4 月进行分析。
使用诊断时的地址，使用区域剥夺指数（ADI）和经过验证的贝叶斯邻里剥夺指数以及种族隔离指数（RI）和历史红线来应用于参与者的地址。使用电子病历确定自我报告的种族。
使用线性回归对每个邻里指标评估了总共 105 个应激相关基因，调整了种族、年龄和手术年份。包括保守的逆境转录反应（CTRA）和应激相关信号基因中的基因。
共纳入 218 名男性（168 [77%] 为非裔美国人，50 [23%] 为白人），中位（IQR）年龄为 58（53-63）岁。非裔美国参与者经历了更大的邻里劣势，而非裔美国参与者的 ADI 中位数（IQR）为 115 [100-130]，而白种参与者的 ADI 中位数（IQR）为 92 [83-104]；RI 中位数（IQR）为 0.68 [0.34-0.87]，而白种参与者的中位数（IQR）为 0.11 [0.06-0.14]。ADI 与 11 个基因的表达呈正相关；在进行多次比较调整后，HTR6（5-羟色胺途径）仍然具有统计学意义（β=0.003；SE，0.001；P<0.001；Benjamini-Hochberg q 值=0.01）。一些基因，包括 HTR6，与多个指标有关。我们观察到，在 CTRA 中，与邻里劣势相关的 5 个促炎基因的表达更高（例如，CXCL8 和 ADI，β=0.008；SE，0.003；P=0.01；q 值=0.21）。
在这项横断面研究中，居住在贫困社区的男性前列腺肿瘤中应激相关基因的表达更高。这项研究是第一个表明邻里劣势与前列腺肿瘤 RNA 表达之间存在关联的研究之一。需要在更大的研究中进行更多研究，以复制研究结果，并进一步研究邻里因素、肿瘤生物学和侵袭性前列腺癌之间的相互关系，为减少差异提供信息干预。
