Background: Breast cancer outcomes are worse among Black women in the U.S. compared to White women. While extensive research has focused on risk factors contributing to breast cancer; the role of genomic elements in health disparities between these racial groups remains unclear. This study aims to identify genomic variants and socioeconomic status (SES) determinants influencing racial disparities in breast cancer survival through multiple mediation analyses.Methods: Our investigation is based on the NIH-supported All of Us (AoU) program and analyzes 7452 female participants with malignant tumors of breast, including 5073 with genomic data. A log-rank test reveals significant racial differences in overall survival time between Black and White participants (p-value = 0.04). Multiple mediation analysis examines the effects of 9481 genetic variables across 23 chromosomes in explaining the racial disparity in survival, adjusting for SES variables.Results: 15 gene mutations, in addition to age, general health, and general quality of life, have significant effects (p-values < 0.001) in explaining the observed racial disparity. Mutations in TMEM132B, NARFL, SALL1, PAD12, RIPK1, ASB14, DCX, GNB1L, ARHGAP32, AL135787.1, WBP11, SLC16A12AS1, AP000345.1, IKBKB, and SUPT20H have significantly different distributions between Black and White participants. The disparity is completely explained by the included variables as the direct effect is insignificant (p-value = 0.73).Conclusions: The combined impact of SES determinants and genetic mutations can explain the observed differences in breast cancer survival among Black and White participants. Future studies will explore pathways and design in vivo and in vitro experiments to validate the functions of these genes
背景：在美国，黑人女性乳腺癌患者的预后较白人女性更差。尽管已有大量研究聚焦于乳腺癌的风险因素，但基因组因素在种族间健康差异中的作用仍不明确。本研究旨在通过多重中介分析，识别影响乳腺癌生存率种族差异的基因组变异及社会经济地位（SES）决定因素。 方法：本研究基于美国国立卫生研究院支持的“全民健康研究”项目，分析了7452名女性乳腺癌恶性肿瘤参与者，其中5073人具有基因组数据。对数秩检验显示，黑人与白人参与者的总生存时间存在显著种族差异（p值=0.04）。通过多重中介分析，在调整SES变量的基础上，检验了23条染色体上9481个遗传变量对生存率种族差异的解释作用。 结果：除年龄、总体健康状况和总体生活质量外，15种基因突变对观察到的种族差异具有显著解释作用（p值<0.001）。TMEM132B、NARFL、SALL1、PAD12、RIPK1、ASB14、DCX、GNB1L、ARHGAP32、AL135787.1、WBP11、SLC16A12AS1、AP000345.1、IKBKB和SUPT20H基因突变在黑人参与者与白人参与者中的分布存在显著差异。由于直接效应不显著（p值=0.73），所纳入变量可完全解释该生存率差异。 结论：社会经济地位决定因素与基因突变的共同作用能够解释黑人与白人参与者乳腺癌生存率的观察差异。未来研究将深入探索相关通路，并通过体内外实验验证这些基因的功能。
肿瘤(癌症)患者之家