Association of mitochondrial DNA variations with lung cancer risk in a Han Chinese population from southwestern China.
Association of mitochondrial DNA variations with lung cancer risk in a Han Chinese population from southwestern China.
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中国西南汉族人群线粒体 DNA 变异与肺癌风险的关联
DOI：
10.1371/journal.pone.0031322
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Ji F
中科院分区：
文献类型：
--
作者：
Zheng S;Qian P;Li F;Qian G;Wang C;Wu G;Li Q;Chen Y;Li J;Li H;He B;Ji F
由于线粒体中活性氧 (ROS) 产生率高且 DNA 修复能力有限，线粒体 DNA (mtDNA) 特别容易受到氧化损伤和突变的影响。先前的研究表明，与吸烟相关的补偿损伤的线粒体DNA拷贝数增加，已被发现与重度吸烟者的肺癌风险相关。鉴于常见的“非病理性”mtDNA 变异决定了氧化磷酸化性能和 ROS 产生的差异（肺癌风险的重要决定因素），我们假设 mtDNA 变异可能在肺癌风险中发挥作用。为了检验这一假设，我们进行了一项病例对照研究，比较 422 名肺癌患者和 504 名对照者之间 mtDNA 单倍群和 822 bp mtDNA 缺失的频率。多变量logistic回归分析显示，单倍群D和F与个体肺癌耐药性相关（OR = 0.465，95%CI = 0.329–0.656，p<0.001；OR = 0.622，95%CI = 0.425–0.909， p = 0.014），而单倍群 G 和 M7 可能是肺癌的危险因素（OR = 3.924，95%CI = 1.757–6.689，p<0.001；OR = 2.037， 95%CI = 1.253–3.312，p = 0.004，分别）。此外，多变量逻辑回归分析显示吸烟是 822 bp mtDNA 缺失的危险因素。此外，单倍群 D 组合病例和对照的男性吸烟受试者中 mtDNA 缺失频率增加表明，单倍群 D 可能容易受到大量吸烟引起的外部 ROS 造成的 DNA 损伤。
Mitochondrial DNA (mtDNA) is particularly susceptible to oxidative damage and mutation due to the high rate of reactive oxygen species (ROS) production and limited DNA-repair capacity in mitochondrial. Previous studies demonstrated that the increased mtDNA copy number for compensation for damage, which was associated with cigarette smoking, has been found to be associated with lung cancer risk among heavy smokers. Given that the common and “non-pathological” mtDNA variations determine differences in oxidative phosphorylation performance and ROS production, an important determinant of lung cancer risk, we hypothesize that the mtDNA variations may play roles in lung cancer risk. To test this hypothesis, we conducted a case-control study to compare the frequencies of mtDNA haplogroups and an 822 bp mtDNA deletion between 422 lung cancer patients and 504 controls. Multivariate logistic regression analysis revealed that haplogroups D and F were related to individual lung cancer resistance (OR = 0.465, 95%CI = 0.329–0.656, p<0.001; and OR = 0.622, 95%CI = 0.425–0.909, p = 0.014, respectively), while haplogroups G and M7 might be risk factors for lung cancer (OR = 3.924, 95%CI = 1.757–6.689, p<0.001; and OR = 2.037, 95%CI = 1.253–3.312, p = 0.004, respectively). Additionally, multivariate logistic regression analysis revealed that cigarette smoking was a risk factor for the 822 bp mtDNA deletion. Furthermore, the increased frequencies of the mtDNA deletion in male cigarette smoking subjects of combined cases and controls with haplogroup D indicated that the haplogroup D might be susceptible to DNA damage from external ROS caused by heavy cigarette smoking.
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影响因子：
4.4
作者：
Li, Fu-Xiang;Ji, Fu-Yun;Zheng, Shi-Zhen;Yao, Wei;Xiao, Zhen-Liang;Qian, Gui-Sheng
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Qian, Gui-Sheng
影响因子：
4.7
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影响因子：
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作者：
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通讯作者：
Sukernik, RI
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3.7
作者：
Cai XY;Wang XF;Li SL;Qian J;Qian DG;Chen F;Yang YJ;Yuan ZY;Xu J;Bai Y;Yu SZ;Jin L
通讯作者：
Jin L
影响因子：
7.4
作者：
Cakir, Yavuz;Yang, Zhen;Ballinger, Scott W.
通讯作者：
Ballinger, Scott W.