Mitochondrial DNA and Cancer Epidemiology
- Funding Opportunities
- Research Resources
- Public Resources
- Selected Publications
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?
There are not currently any specific NCI Requests for Applications (RFAs) or Program Announcements (PAs) for mitochondrial DNA in cancer epidemiology research; however, EGRP encourages investigator-initiated grant applications on these topics.
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.
EGRP also encourages investigator-initiated grant applications studying changes in mitochondrial DNA in relation to cancer epidemiology.
- Human Mitochondrial Genome Database (mtDB)
Download mitochondrial DNA sequences, view polymorphic sites, and search for specific variants.
- Human Mitochondrial Protein Database (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.
Published and unpublished data on human mitochondrial variation.
Integrated data warehouse of proteomic data for mitochondria.
Mitochondrial data sharing research tool.
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 Database (SMFG)
Collection of mitochondrial DNA data and corresponding genealogies from more than 75,000 people throughout the world.
- Genetics Home Reference: Mitochondrial DNA
National Library of Medicine Web page with plain language description of mitochondrial DNA and links to an illustration and additional sources of information.
- Talking Glossary of Genetic Terms: Mitochondrial DNA
National Human Genome Research Institute Web page provides a definition of mitochondria DNA, an illustration, and a 3D animation.
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:
- Huang B, Gao YT, Shu XO, Wen W, Yang G, Li G, Courtney R, Ji BT, Li H, Purdue MP, Zheng W, Cai Q. Association of leukocyte mitochondrial DNA copy number with colorectal cancer risk: results from the Shanghai Women's Health Study. Cancer Epidemiol Biomarkers Prev. 2014 Nov;23(11):2357-65.
- Jiang H, Zhao H, Xu H, Hu L, Wang W, Wei Y, Wang Y, Peng X, Zhou F. Peripheral blood mitochondrial DNA content, A10398G polymorphism, and risk of breast cancer in a Han Chinese population. Cancer Sci. 2014 Jun;105(6):639-45.
- Guo Y, Li CI, Sheng Q, Winther JF, Cai Q, Boice JD, Shyr Y. Very low-level heteroplasmy mtDNA variations are inherited in humans. J Genet Genomics. 2013 Dec 20;40(12):607-15.
- Xu E, Sun W, Gu J, Chow WH, Ajani JA, Wu X. Association of mitochondrial DNA copy number in peripheral blood leukocytes with risk of esophageal adenocarcinoma. Carcinogenesis. 2013 Nov;34(11):2521-4. Erratum in: Carcinogenesis. 2014 Mar;35(3):738.
- Lascorz J, Bevier M, Schönfels WV, Kalthoff H, Aselmann H, Beckmann J, Egberts J, Buch S, Becker T, Schreiber S, Hampe J, Hemminki K, Försti A, Schafmayer C. Polymorphisms in the mitochondrial oxidative phosphorylation chain genes as prognostic markers for colorectal cancer. BMC Med Genet. 2012 Apr 30;13:31.
- Guney AI, Ergec DS, Tavukcu HH, Koc G, Kirac D, Ulucan K, Javadova D, Turkeri L. Detection of mitochondrial DNA mutations in nonmuscle invasive bladder cancer. Genet Test Mol Biomarkers. 2012 Jul;16(7):672-8.
To learn more about recent research findings on basic mechanisms in mitochondrial biology, the following journals may be of interest:
- Mitochondrion: The journal covers mitochondria related publications, conference/meeting updates, and the latest information from the Mitochondria Research Society
- Mitochondrial Research: This journal is dedicated to publishing and disseminating new and significant findings involving the role of mitochondria in cell physiology and pathology.
EGRP is not sponsoring any meetings or conferences on mitochondrial DNA and cancer epidemiology in the near future; however, interested investigators are encouraged to learn about upcoming scientific meetings and conferences that are relevant to this area of research through journals, such as Mitochondrion.
- Mitochondrial DNA and Cancer Epidemiology (September 2006)
For general questions about mitochondrial DNA in cancer epidemiology research, contact EGRP's Mukesh Verma, Ph.D., Chief, Methods and Technologies Branch.