Mitochondrial DNA and Cancer Epidemiology


Figure: Mitomap representing gene location and mtDNA mutations detected in different cancers. The large multi-colored circle shown here represents the mitochondrial genome. The colored boxes along the circle represent specific genes. The blue boxes with white letters represent the haplogroups. Various cancers associated with the individual genes are represented by the following abbreviations: Bl = Bladder Cancer, Br = Breast Cancer, Co = Colorectal Cancer, H & N = Head and Neck Cancer, Ov = Ovarian Cancer, Pa = Pancreatic Cancer, Pr = Prostate Cancer, and Th = Thyroid Cancer.<br/><br/>
<em>Reprinted from Clinica Chimica Acta, Volume 383, Issue 1-2, Mukesh Verma and Deepak Kumar, Application of mitochondria genome information in cancer epidemiology [], pages 41-50, Copyright 2007, with permission from Elsevier.</em>

Mitimap Illustration
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Mitochondria play an important role in cellular energy metabolism, free radical generation, and apoptosis. At some point during neoplastic transformation, an increase in reactive oxygen species damages the mitochondrial genome. This increase accelerates the somatic mutation rate of mitochondrial DNA (mtDNA). These mutations may represent a means for tracking tumor progression.

Mitochondria contain their own genome (16.5 kb) along with transcription, translation, and protein assembly machinery. They are able to maintain genomic independence from the nucleus. Somatic mutations have been reported in different tumor types, and some reports indicate inherited mitochondrial DNA polymorphisms in cancer. Mutations have been detected in mitochondria in various tumor types, including breast, colon, esophageal, endometrial, head and neck, liver, kidney, lung, oral, prostate, and thyroid cancer, and melanoma and leukemia.

Specific scientific questions of interest to EGRP are:

  • Will inclusion of mitochondrial markers help to identify new risk factors (modifiable factors, host factors) in different races and ethnic groups?
  • Will mitochondrial markers in cohort and case-control studies improve their sensitivity and specificity and help identify high-risk populations?
  • Are genetic and mitochondrial DNA alterations (somatic mutations, deletions) correlated during cancer development?
  • Can we utilize mitochondrial haplogroup information to identify high-risk populations?
  • How can we utilize mitochondrial proteomic information to understand gene-gene and gene-environment studies and cancer etiology?

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Funding Opportunities

NCI-sponsored Funding Opportunity Announcements (FOA) related to mitochondrial DNA in cancer epidemiology include:

  • Mitochondria in Cancer Epidemiology, Detection, Diagnosis, and Prognosis - expires January 8, 2014, unless reissued

EGRP joins with other NCI Divisions, Offices, and Centers and other Institutes and Centers at the National Institutes of Health (NIH) to fund grant applications submitted in response to FOAs.

View the full list of EGRP FOAs.

EGRP also encourages investigator-initiated grant applications studying changes in mitochondrial DNA in relation to cancer epidemiology.

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Funded Projects

View a list of active projects involving mtDNA supported by the Epidemiology and Genomics Research Program (EGRP) in NCI's Division of Cancer Control and Population SciencesExternal Web Site Policy.

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Mitochondrial DNA is the small circular chromosome found inside mitochondria. The mitochondria are organelles found in cells that are the sites of energy production. The mitochondria, and thus mitochondrial DNA, are passed from mother to offspring.<br/><br/><em>National Institutes of Health. National Human Genome Research Institute. 'Talking Glossary of Genetic Terms.' Retrieved April 25, 2012, from</em>

Cross Section of
Mitochondrial DNA

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Research Resources

  • Human Mitochondrial Genome DatabaseExternal Web Site Policy (mtDB)
    Download mitochondrial DNA sequences, view polymorphic sites, and search for specific variants.
  • Human Mitochondrial Protein DatabaseExternal Web Site Policy (HMPDb)
    National Institute of Standards and Technologies (NIST) database with comprehensive data on mitochondrial and human nuclear encoded proteins involved in mitochondrial biogenesis and function.
  • MITOMAPExternal Web Site Policy
    Published and unpublished data on human mitochondrial variation.
  • MitoMinerExternal Web Site Policy
    Integrated data warehouse of proteomic data for mitochondria.
  • MITOWIKIExternal Web Site Policy
    Mitochondrial data sharing research tool.
  • PhyloTreeExternal Web Site Policy
    A phylogenetic tree of global human mitochondrial DNA variation, based on both coding- and control-region mutations, and including haplogroup nomenclature.
  • Sorenson Molecular Genealogy Foundation Mitochondrial DatabaseExternal Web Site Policy (SMFG)
    Collection of mitochondrial DNA data and corresponding genealogies from more than 75,000 people throughout the world.

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Public Resources

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Selected Publications

Tools to characterize and measure mtDNA characteristics are now available that can be used on the types of biospecimens available in epidemiologic studies, and are sufficiently high throughput for the large numbers of samples analyzed in population-based studies. The following selected publications discuss measurement of mtDNA alterations in cancer epidemiology research:

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EGRP co-sponsors workshops and meetings to convene experts in the fields of cancer epidemiology and environmental research to review the state-of-the-science, identify research gaps, and establish scientific agendas/priorities for the future, such as:

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For general questions about mitochondrial DNA in cancer epidemiology research, contact EGRP's Mukesh Verma, Ph.D., Chief, Methods and Technologies Branch.

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