Cancer Epidemiology

Volume 471 of the series Methods in Molecular Biology pp 291-303

Mitochondrial DNA Polymorphism and Risk of Cancer

  • Keshav K. SinghAffiliated withDepartment of Cancer Genetics, Roswell Park Cancer Institute
  • , Mariola KulawiecAffiliated withDepartment of Cancer Genetics, Roswell Park Cancer Institute

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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, devel opment, 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 polymor phisms in mtDNA and in nuclear DNA.

Key words

Apoptosis mitochondria oxidative phosphorylation polymorphism reactive oxygen species