Mitochondrial DNA polymorphism and risk of cancer.
Mitochondrial DNA polymorphism and risk of cancer.
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DOI：
10.1007/978-1-59745-416-2_15
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发表时间：
2009
期刊：
影响因子：
--
通讯作者：
Kulawiec, Mariola
中科院分区：
文献类型：
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作者：
Singh, Keshav K;Kulawiec, Mariola
ATP（能量生产）不是线粒体的唯一功能。线粒体执行多种细胞功能。其中，这些功能包括控制细胞死亡、生长、发育、从线粒体到细胞核和细胞核到线粒体的信号整合以及各种代谢途径。虽然线粒体功能的缺陷最常与生物能缺陷相关，但我们的研究表明，线粒体缺陷导致核DNA中的基因组不稳定性、对细胞凋亡的抵抗和NADPH氧化酶（活性氧的指定生产者）的诱导。细胞表型的这些转化是已知的人类肿瘤发展的贡献者。与线粒体在癌症发生中的作用一致，过去几年的研究已经描述了与人类群体中各种不同单倍型群中特定线粒体DNA（mtDNA）多态性相关的癌症风险增加。然而，由于特定的mtDNA多态性导致癌症风险增加的分子机制目前尚不清楚。线粒体电子传递链和氧化磷酸化相关基因的mtDNA多态性可能导致线粒体和核DNA的氧化应激和超突变增加。我们建议，在癌症流行病学研究中，特定mtDNA多态性的意义应与mtDNA和核DNA中的其他多态性一起分析。
ATP (energy production) production is not the only function of the mitochondria. Mitochondria perform multiple cellular functions. Among others, these functions include control of cell death, growth, development, integration of signals from mitochondria to nucleus and nucleus to mitochondria, and various metabolic pathways. Although defects in mitochondrial function are most commonly associated with bioenergetic deficiencies, our studies demonstrate that mitochondrial defects lead to genome instability in the nuclear DNA, resistance to apoptosis and induction of NADPH oxidase, a designated producer of reactive oxygen species. These transformations in cellular phenotype are known contributors to the development of tumors in humans. Consistent with the role of mitochondria in carcinogenesis, studies in the past few years have described an increased risk of cancers associated with specific mitochondrial DNA (mtDNA) polymorphism among various different haplogroups in human population. However, molecular mechanisms underlying increased risk of cancer due to specific mtDNA polymorphisms is currently lacking. It is likely that mtDNA polymorphisms in mitochondrial genes involved in electron transport chain and oxidative phosphorylation result in increased oxidative stress and hypermutagenesis of mitochondrial as well as nuclear DNA. We suggest that in studies relating to cancer epidemiology, the significance of a particular mtDNA polymorphism(s) should be analyzed together with other polymorphisms in mtDNA and in nuclear DNA.