Peripheral blood leukocyte mitochondrial DNA content and risk of lung cancer.
Peripheral blood leukocyte mitochondrial DNA content and risk of lung cancer.
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外周血白细胞线粒体DNA含量与肺癌发病风险的关系
DOI：
10.21037/tlcr-21-979
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发表时间：
2022-07
影响因子：
4
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中科院分区：
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以往关于外周血白细胞线粒体DNA （mtDNA）含量与肺癌风险的研究得出了不一致的结果，没有研究评估mtDNA含量与肺癌切除术后预后之间的关系。采用病例对照研究设计，我们评估了465例病例和378例对照的mtDNA含量与肺癌风险之间的关系。我们还评估了189例手术切除的非小细胞肺癌（NSCLC）患者mtDNA含量与生存率之间的关系。采用实时定量聚合酶链反应（PCR）测定外周血基因组DNA的相对mtDNA含量。我们使用多变量逻辑回归计算优势比（ORs）和95%置信区间（ci），调整了年龄、性别、种族和吸烟史。与对照组相比，病例mtDNA含量较低，中位数分别为1.26[四分位间距（IQR）， 0.98-1.70]和1.79 （IQR, 1.34-2.10， P<0.001）。与mtDNA含量最高的四分位数相比，第二低四分位数（OR 3.44; 95% CI: 2.06-5.75）和最低四分位数（OR 6.36; 95% CI: 3.86-10.47）患肺癌的可能性明显更高。在切除的NSCLC患者中，mtDNA含量较低与无复发生存率（RFS）无关联[危险比（HR） 0.89；95% CI: 0.47-1.66]或总生存率（OS） （HR 0.71; 95% CI: 0.35-1.46）。因此，我们的结果与之前的研究相反，发现较低的mtDNA含量与肺癌风险有关。我们的研究结果表明，mtDNA含量可能作为一种潜在的风险生物标志物，但与NSCLC的生存结果无关。
Previous studies of peripheral blood leukocyte mitochondrial DNA (mtDNA) content and risk of lung cancer have yielded inconsistent results, and no studies have evaluated the association between mtDNA content and post-resection lung cancer outcomes. Using a case-control study design, we evaluated the association between mtDNA content and risk of lung cancer in 465 cases and 378 controls. We also evaluated the association between mtDNA content and survival in 189 cases with surgically resected non-small cell lung cancer (NSCLC). Relative mtDNA content was measured using a quantitative real-time polymerase chain reaction (PCR) assay in peripheral blood genomic DNA. We calculated odds ratios (ORs) and 95% confidence intervals (CIs) using multivariable logistic regression, adjusting for age, gender, race, and smoking history. mtDNA content was lower in cases compared to controls, with medians of 1.26 [interquartile range (IQR), 0.98–1.70)] and 1.79 (IQR, 1.34–2.10; P<0.001), respectively. Compared to the quartile of subjects with the highest mtDNA content, there was significantly higher likelihood of lung cancer in the second lowest quartile (OR 3.44; 95% CI: 2.06–5.75) and the lowest quartile (OR 6.36; 95% CI: 3.86–10.47). In patients with resected NSCLC, there was no association between lower mtDNA content and recurrence-free survival (RFS) [hazard ratio (HR) 0.89; 95% CI: 0.47–1.66] or overall survival (OS) (HR 0.71; 95% CI: 0.35–1.46). Thus, our results counter previous studies and find that lower mtDNA content is associated with lung cancer risk. Our results suggest that mtDNA content could potentially serve as a risk biomarker, but is not associated with survival outcomes in NSCLC.