Prevention Research Using Genetic Information to Prevent Disease and Improve Health
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Office of Public Health Genomics, CDC
In May 1999, the Office of Public Health Genomics, CDC, announced the availability of $700,000 to support new extramural research in two categories:
- Epidemiologic research–to assess the interaction of modifiable risk factors (e.g., diet, chemical exposures, infections, lifestyle) with known genetic disease risk factors, and to demonstrate how this information can help target disease prevention efforts.
- Prevention effectiveness research–to demonstrate the effectiveness of using genetic information to prevent disease, disability and death by finding persons at risk and carrying out appropriate interventions.
Research proposals in either category could address cardiovascular disease, cancer, arthritis, diabetes, or pediatric pulmonary disease (asthma, cystic fibrosis), which are among the leading causes of mortality, morbidity, and disability in the U.S., and have identifiable genetic and environmental risk factors.
These funds were made available as part of CDC’s Prevention Research Initiative, an effort to link the talents and skills of university-based scientists with the resources of health departments, community-based programs, and national organizations. Thirteen research proposals were received and reviewed by a special emphasis panel including experts from a wide range of disciplines and institutions.
The two top-ranked proposals selected for funding were:
Principal Investigator: Molly S. Bray, University of Texas, Houston, Texas
The investigators are using stored DNA from the multi-center Atherosclerosis Risk in Communities (ARIC) Study to examine gene-environment interactions related to cardiovascular disease in 15,564 African American and white men and women aged 45-64 years. The study will evaluate genetic polymorphisms related to lipid metabolism, obesity and blood pressure. Environmental factors will include nutrition, body mass index, physical activity, smoking, and hormone use; clinical endpoints will include total cholesterol, HDL cholesterol, LDL cholesterol, total triglycerides, body mass index, waist hip ratio, systolic and diastolic blood pressure, and incident coronary heart disease and stroke. Gene-environment interactions will be assessed in race-gender specific groups for effects on quantitative cardiovascular disease risk factors, subclinical disease (carotid artery wall thickness), and incidence of coronary heart disease and stroke.
Principal Investigator: Peter T. Rowley, University of Rochester, Rochester, New York
This project will examine whether it is preferable to direct educational efforts to the high risk cancer patient or to his or her physician. Colorectal cancer was chosen for study because it is the second most common cause of cancer death, a significant fraction of cases appears to be initiated by an inherited mutation, individuals at high risk can be identified by DNA analysis, and intensive surveillance started at an early age can usually prevent a fatal outcome. The investigators will identify index colorectal patients diagnosed at #55 years of age who have a family history of colorectal cancer, randomize them to a physician education group or to a patient education group, and offer genetic counseling and DNA testing to the index patient either via the physician of record or directly. They will make recommendations for clinical surveillance based on clinical features, inheritance pattern, and (if patient elects DNA testing) the test result, offer first-degree adult relatives both counseling and (if the index patient has a detected mutation) and DNA testing, and conduct follow-up interviews with patients, referred relatives, and their physicians. Major outcomes will be proportion of index patients coming for counseling, proportion choosing DNA testing, proportion following surveillance recommendations, and proportion referring relatives for counseling.
In September 2000, a third project was funded with support from the Division of Laboratory Sciences, NCEH, CDC:
Principal Investigator: William A. Hagopian, Pacific Northwest Research Institute, Seattle, Washington
The investigators will ask parents of 4-year-olds for permission to test their children’s stored newborn screening samples (dried-blood spots) for genetic markers associated with risk for developing juvenile diabetes. Children with combinations of markers that place them in the 20% at highest risk for developing diabetes will be offered the opportunity to participate in a follow-up study. The follow-up study will measure autoantibodies associated with progression to diabetes at 3-year intervals until the child reaches adolescence. Children whose sequential autoantibody test results suggest a high risk of developing diabetes will be offered enrollment in clinical prevention trials of FDA-approved therapies designed to interrupt disease progression.
Together, these projects offer good balance with respect to research category and condition, as well as geography and age and racial/ethnic diversity of study populations. They complement ongoing work within the CDC Divisions concerned with cardiovascular disease, cancer, and diabetes. In addition to carrying out the funded projects, the investigators represent a resource to CDC in the area of genetics.