Non-Hispanic Black breast cancer survivors have poorer outcomes and higher mortality rates than White survivors, but systemic biological mechanisms underlying these disparities are unclear. We used circulating leukocytes as a surrogate for measuring systemic mechanisms, which might be different from processes in the target tissue (e.g., breast). We investigated race-based differences in DNA damage and repair, using a novel CometChip assay, in circulating leukocytes from breast cancer survivors who had completed primary cancer therapy and were cancer free. We observed novel race-based differences in systemic DNA damage and repair activity in cancer survivors, but not in cells from healthy volunteers. Basal DNA damage in leukocytes was higher in White survivors, but Black survivors showed a much higher induction after bleomycin treatment. Double-strand break repair activity was also significantly different between the races, with cells from White survivors showing more sustained repair activity compared to Black leukocytes. These results suggest that cancer and cancer therapy might have long-lasting effects on systemic DNA damage and repair mechanisms that differ in White survivors and Black survivors. Findings from our preliminary study in non-cancer cells (circulating leukocytes) suggest systemic effects beyond the target site, with implications for accelerated aging-related cancer survivorship disparities.
非西班牙裔黑人乳腺癌幸存者相较于白人幸存者预后更差、死亡率更高，但造成这种差异的系统性生物学机制尚不明确。本研究以循环白细胞作为系统性机制的替代测量指标，这些机制可能与靶组织（如乳腺）中的过程存在差异。我们采用新型彗星芯片检测技术，对已完成主要癌症治疗且无癌生存的乳腺癌幸存者循环白细胞中的DNA损伤与修复进行了种族差异性研究。研究发现，在癌症幸存者中（而非健康志愿者细胞中）存在显著的种族特异性系统性DNA损伤与修复活性差异。白人幸存者白细胞的基础DNA损伤水平较高，但黑人幸存者在博来霉素处理后表现出更强的DNA损伤诱导效应。双链断裂修复活性在种族间也存在显著差异，白人幸存者的细胞表现出比黑人白细胞更持久的修复活性。这些结果表明，癌症及其治疗可能对白人幸存者和黑人幸存者的系统性DNA损伤与修复机制产生具有种族差异的长期影响。我们在非癌细胞（循环白细胞）中的初步研究结果提示，这种影响可能超越靶组织范围，对加速衰老相关的癌症幸存者健康差异具有重要启示。
Systemic DNA Damage and Repair Activity Vary by Race in Breast Cancer Survivors
肿瘤(癌症)患者之家