Cancer-related fatigue (CRF) is characterized by a lack of energy, and mitochondrial dysfunction is postulated to contribute to its etiology. This prospective cohort study assesses the self-reported fatigue levels of early-stage breast cancer patients using the validated Multi-Dimensional Fatigue Symptom Inventory-Short Form (MFSI-SF) and blood samples drawn at three time points: before treatment, approximately 6 weeks, and 12 weeks after the initiation of chemotherapy. The aim of this study is to evaluate mitochondrial measures with CRF, over the course of chemotherapy using mitochondrial DNA (mtDNA content) and displacement loop (D-loop) region sequence variations at nucleotide positions 303, 489 and 514. The relative mtDNA copy number was determined via real-time quantitative polymerase chain reaction and compared between study time points and D-loop sequence variants. The association of mtDNA content with MFSI-SF total and sub-domain scores was analyzed in a sample of 155 patients (mean age ± SD: 51.7 ± 8.8 years). The median mtDNA content decreased over 12 weeks after the initiation of chemotherapy (p < 0.001). Baseline mtDNA content was lower for nucleotide position 303 in sequence variations than for the reference sequence (67.2 copies vs 79.1 copies, p = 0.03). Physical fatigue negatively correlated with mtDNA content in both unadjusted (β = -0.0075, p= 0.048) and adjusted models (β = -0.0062, p= 0.042), accounting for age, anxiety, insomnia, haemoglobin levels and body mass index. Our findings add to the literature indicating that mitochondrial function serves as an important target for mitigating CRF.

中文翻译：

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接受化疗的乳腺癌幸存者的线粒体 DNA 含量和置换环区序列变异与癌症相关疲劳的关联

癌症相关疲劳 (CRF) 的特点是缺乏能量，推测其病因是线粒体功能障碍。这项前瞻性队列研究使用经过验证的多维疲劳症状清单 - 简表 (MFSI-SF) 和在三个时间点抽取的血液样本评估早期乳腺癌患者自我报告的疲劳水平：治疗前，大约 6 周，以及化疗开始后 12 周。本研究的目的是在化疗过程中使用线粒体 DNA（mtDNA 含量）和置换环（D-loop）区域序列变异在核苷酸位置 303、489 和 514 上评估 CRF 的线粒体测量值。通过实时定量聚合酶链反应确定相对 mtDNA 拷贝数，并在研究时间点和 D 环序列变体之间进行比较。在 155 名患者的样本中分析了 mtDNA 含量与 MFSI-SF 总分和子域评分的关联（平均年龄 ± SD：51.7 ± 8.8 岁）。化疗开始后 12 周内 mtDNA 含量中位数下降（p < 0.001）。序列变异中核苷酸位置 303 的基线 mtDNA 含量低于参考序列（67.2 拷贝 vs 79.1 拷贝，p = 0.03）。身体疲劳与未调整 (β = -0.0075, p= 0.048) 和调整后模型 (β = -0.0062, p= 0.042) 中的 mtDNA 含量呈负相关，考虑了年龄、焦虑、失眠、血红蛋白水平和体重指数。