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Telomere length, mitochondrial DNA mass, and risk for major chronic diseases

Principal Investigator
Name
Richard Hayes
Degrees
-
Institution
New York University
Position Title
-
Email
About this CDAS Project
Study
PLCO (Learn more about this study)
Project ID
2005-0006
Initial CDAS Request Approval
Aug 17, 2005
Title
Telomere length, mitochondrial DNA mass, and risk for major chronic diseases
Summary
Data from small cohort and retrospective case-control studies suggests that cancer and heart disease risks are predicted by shorter telomere length, measured in peripheral blood DNA (buffy coat). Mitochondrial dysfunction, related to oxidative stress, may also be an important, but less studied, determinant of these diseases. Telomere length and mtDNA mass may serve as integrative biomarkers of individual response to the effects of long-term oxidative damage, at the cellular level. Polymorphisms in mitochondrial maintenance genes may be determinants of ROS-related prostate cancer (Petros et al, 2005) and other diseases. We plan a large-scale prospective evaluation in the PLCO Trial of risk for major causes of mortality in relation to telomere length and mtDNA mass. The study will evaluate telomere length, mtDNA mass and associated gene variants as predictive risk factors (taking age and tobacco use into account) for:
Death due to heart disease (n=300)
Incidence of Lung cancer (n=300)
Incidence of Prostate cancer (n=300)
Incidence of Lymphoma (n= 200)
Incidence of Leukemia (n=150).
The disease sites chosen include major causes of death, of which two diseases have been related in small studies to telomere length (heart disease and lung cancer), one of which is strongly (chronologic-) age related (prostate cancer), and two of which are hematopoietic in origin (lymphoma).
Aims

Data from small cohort and retrospective case-control studies suggests that cancer and heart disease risks are predicted by shorter telomere length, measured in peripheral blood DNA (buffy coat). Mitochondrial dysfunction, related to oxidative stress, may also be an important, but less studied, determinant of these diseases. Telomere length and mtDNA mass may serve as integrative biomarkers of individual response to the effects of long-term oxidative damage, at the cellular level. Polymorphisms in mitochondrial maintenance genes may be determinants of ROS-related prostate cancer (Petros et al, 2005) and other diseases. We plan a large-scale prospective evaluation in the PLCO Trial of risk for major causes of mortality in relation to telomere length and mtDNA mass. The study will evaluate telomere length, mtDNA mass and associated gene variants as predictive risk factors (taking age and tobacco use into account) for: Death due to heart disease (n=300). Incidence of Lung cancer (n=300). Incidence of Prostate cancer (n=300). Incidence of Lymphoma (n= 200). Incidence of Leukemia (n=150). The disease sites chosen include major causes of death, of which two diseases have been related in small studies to telomere length (heart disease and lung cancer), one of which is strongly (chronologic-) age related (prostate cancer), and two of which are hematopoietic in origin (lymphoma).

Collaborators

S. Chanock (NCI, CCR)
Richard Hayes (NCI, DCEG)
Q. Lan (NCI, DCEG)
R. Cawthon (University of Utah)
N. Rothman (NCI, DCEG)
R. Vermeulen (NCI, DCEG)

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