Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA; Department of Epidemiology, Richard M. Fairbanks School of Public Health, Indiana University, Indianapolis, IN, USA.
Department of Nutrition Science, College of Health and Human Science, Purdue Center for Cancer Research, Purdue University, West Lafayette, IN, USA.
Cancer Epidemiol. 2020 Oct;68:101778. doi: 10.1016/j.canep.2020.101778. Epub 2020 Jul 14.
Mitochondrial DNA copy number (mtDNAcn) is considered a biomarker for mitochondrial function and oxidative stress. Although previous studies have suggested a potential relationship between mtDNAcn at the time of colorectal cancer (CRC) diagnosis and CRC prognosis, findings have been inconsistent, and no study has specifically investigated the association of pre-diagnostic mtDNAcn with CRC survival.
We examined the association of pre-diagnostic leukocyte mtDNAcn (measured by qPCR) with overall and CRC-specific survival among 587 patients in Nurses' Health Study and Health Professionals Follow-Up Study. Cox models were constructed to estimate hazard ratios (HRs) and 95 % confidence intervals (95 % CIs).
During a mean follow-up of 10.5 years, 395 deaths were identified; 180 were due to CRC. Overall, we did not observe significant associations between mtDNAcn and either overall or CRC-specific survival among all cases or by cancer location, grade, or stage. In an exploratory stratified analysis, a suggestive inverse association of mtDNAcn and overall death risk appeared among current smokers [HR (95 % CI) for 1 SD decrease in mtDNAcn = 1.50 (0.98, 2.32), P-trend = 0.06]. Reduced mtDNAcn and lower CRC-specific death risk was observed among patients aged ≤ 70.5 at diagnosis [HR (95 % CI) for 1 SD decrease of mtDNAcn = 0.71 (0.52, 0.97), P-trend = 0.03], ≤ 5 years from blood collection to diagnosis [HR (95 % CI) for 1 SD decrease in mtDNAcn = 0.65 (0.44, 0.96), P-trend = 0.03] and those consuming a low-inflammatory diet [HR (95 % CI) for 1 SD decrease in mtDNAcn = 0.61 (0.42, 0.88), P-trend = 0.009].
no significant associations between pre-diagnostic leukocyte mtDNAcn and either overall or CRC-specific survival appeared but exploratory analysis identified potential sub-group associations.
线粒体 DNA 拷贝数（mtDNAcn）被认为是线粒体功能和氧化应激的生物标志物。尽管先前的研究表明结直肠癌（CRC）诊断时 mtDNAcn 与 CRC 预后之间存在潜在关系，但研究结果不一致，并且没有研究专门探讨预诊断 mtDNAcn 与 CRC 生存的关系。
我们检查了白细胞预诊断 mtDNAcn（通过 qPCR 测量）与护士健康研究和健康专业人员随访研究中的 587 例患者的总体生存率和 CRC 特异性生存率之间的关系。构建 Cox 模型来估计风险比（HR）和 95 %置信区间（95 %CI）。
在平均 10.5 年的随访期间，确定了 395 例死亡病例；其中 180 例死于 CRC。总体而言，我们没有发现 mtDNAcn 与所有病例或按癌症位置、分级或分期的总体生存率或 CRC 特异性生存率之间存在显著关联。在探索性分层分析中，mtDNAcn 与全因死亡风险呈负相关的趋势在当前吸烟者中出现[mtDNAcn 降低 1 个标准差的 HR（95 %CI）= 1.50（0.98，2.32），P 趋势= 0.06]。在诊断时年龄≤70.5 岁的患者中，mtDNAcn 降低与较低的 CRC 特异性死亡风险相关[mtDNAcn 降低 1 个标准差的 HR（95 %CI）= 0.71（0.52，0.97），P 趋势= 0.03]，距采血至诊断的时间≤5 年的患者[mtDNAcn 降低 1 个标准差的 HR（95 %CI）= 0.65（0.44，0.96），P 趋势= 0.03]和饮食炎症程度低的患者[mtDNAcn 降低 1 个标准差的 HR（95 %CI）= 0.61（0.42，0.88），P 趋势= 0.009]。
白细胞预诊断 mtDNAcn 与总体生存率或 CRC 特异性生存率之间无显著关联，但探索性分析确定了潜在的亚组关联。
