Mitochondrial DNA copy number and lung cancer risk in a prospective cohort study
Mitochondrial DNA copy number and lung cancer risk in a prospective cohort study
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DOI：
10.1093/carcin/bgq045
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发表时间：
2010-05-01
期刊：
影响因子：
4.7
通讯作者：
Lan, Qing
中科院分区：
文献类型：
--
作者：
Hosgood, H. Dean, III;Liu, Chin-San;Lan, Qing
线粒体是真核生物中负责能量产生的细胞器。线粒体DNA （mtDNA）缺乏内含子和保护性组蛋白，DNA修复能力有限，通过增加mtDNA拷贝数来补偿损伤。因此，线粒体更容易受到活性氧的影响，而活性氧是癌症风险的重要决定因素。据推测，mtDNA拷贝数的增加可能与癌症发生有关。我们评估了来自α -生育酚、β -胡萝卜素癌症预防研究的227例前瞻性收集病例和227例匹配对照的mtDNA拷贝数与肺癌风险的关系。使用条件逻辑回归来估计优势比（ORs）和95%置信区间（ci），调整随机化时的年龄、吸烟年数和每天吸烟的数量。mtDNA拷贝数与随后的肺癌风险之间存在剂量依赖关系，mtDNA拷贝数最高的四分位数[or （95% CI）按四分位数分别为1.0（参考）、1.3（0.7-2.5）、1.1（0.6-2.2）和2.4(1.1-5.1)]显著影响；P-trend = 0.008]。据我们所知，这是第一份在前瞻性队列研究中表明mtDNA拷贝数可能与随后的肺癌风险呈正相关的报告；然而，需要在其他研究和人群中进行复制。
Mitochondria are eukaryotic organelles responsible for energy production. Mitochondrial DNA (mtDNA) lack introns and protective histones, have limited DNA repair capacity and compensate for damage by increasing the number of mtDNA copies. As a consequence, mitochondria are more susceptible to reactive oxygen species, an important determinant of cancer risk, and it is hypothesized that increased mtDNA copy number may be associated with carcinogenesis. We assessed the association of mtDNA copy number and lung cancer risk in 227 prospectively collected cases and 227 matched controls from the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. Conditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs), adjusting for age at randomization, smoking years and number of cigarettes smoked per day. There was suggestion of a dose-dependent relationship between mtDNA copy number and subsequent risk of lung cancer, with a prominent effect observed in the highest mtDNA copy number quartile [ORs (95% CI) by quartile: 1.0 (reference), 1.3 (0.7-2.5), 1.1 (0.6-2.2) and 2.4 (1.1-5.1); P-trend = 0.008]. This is the first report, to the best of our knowledge, to suggest that mtDNA copy number may be positively associated with subsequent risk of lung cancer in a prospective cohort study; however, replication is needed in other studies and populations.