Description
The overall goal of this RFA is to elucidate the role of gene-environment interactions to better understand how environmental exposures affect disease risk. The major focus is on the study of gene-environment interactions in the etiology of cancer and several other environmentally related diseases (asthma, cardiovascular disease, diabetes, and obesity) in human populations.
The Specific Aims of Research Focus Area 1 are:
- To increase our understanding of the contribution of environmental exposures and genetic susceptibility to disease risk (cancer, cardiovascular disease, asthma, diabetes, and obesity).
- To elucidate the role of diet, energy balance, physical activity, and biobehavioral determinants in environmental disease risk.
- To develop novel genotypic and phenotypic assays to improve understanding of risk for cancer and other complex environmental diseases.
- To serve as a consultative and collaborative resource across RFAs and work closely with the Integrative Health Sciences Core to develop concepts for studies, provide human tissues, and environmental data measurement and collection.
Research Significance
The overall goal of RFA1 will be for its members to integrate their research efforts with other clinical and basic CRED researchers to better define both environmental and other risk factors including diet and genetic factors with the ultimate goal to preventing environmentally related diseases such as cancer, asthma, CVD, and diabetes.
Conceptually, research in this RFA can be divided into the following categories: 1) exposure assessment and disease risk; 2) analysis of phenotypic markers of risk; 3) genotypic measures of susceptibility; and 4) diet, energy balance, and physical activity in relation to genetic background and disease risk. Environmental and personal exposures are assessed using multiple approaches including questionnaire (risk factors), quantitative environmental samples to measure indoor and outdoor air toxicants, and biomarkers of exposure (e.g. DNA adducts). RFA1 members have developed and refined a number of phenotypic assays their research projects incorporate, including short-term lymphocyte assays that gauge host susceptibility by measuring induced chromatid breaks after exposure to an array of mutagens, and DNA repair capacity of peripheral lymphocytes, using the host cell reactivation assay with select mutagen challenges, including BPDE and UV radiation. RFA1 members have also evaluated the role of common genetic variants as risk factors for cancer susceptibility and have been focusing on pathways of genes involved in xenobiotic metabolism, DNA repair, cell cycle, inflammation, folate metabolism, hormones and growth factors, and methylation in a variety of cancer sites.
Diet and physical activity impact environmental disease risk significantly, and the related global epidemic of obesity has become a major public health problem, reflected in the incidence of type-II diabetes. Besides diabetes and cardiovascular disease (CVD), overweight and obesity also explains about 15-20% of all U.S. cancer deaths, i.e., about 90,000 deaths annually from cancer. Current trends of poor diet and physical inactivity suggest that they may become the leading causes of death in the U.S. Ongoing population-based studies of cancer risk include evaluation of diet and diet-gene interactions. In addition, a major research effort is the Mexican-American (MA) Cohort study in Harris County, Texas. This cohort offers the unique opportunity to study and evaluate other environmentally related diseases in relationship to obesity.
Epidemiological studies consistently indicate that urban pollution with airborne particulate matter (PM) is associated with increases in daily mortality and morbidity in both respiratory and CVD. Human exposure to environmental PM is consistently linked in epidemiological studies to several adverse cardiovascular outcomes, including mortality, exacerbation of coronary artery disease and cardiac rhythm disturbances, elevations in blood pressure and increased expression of certain blood markers of inflammation and thrombosis. Many, if not most, of the associations observed between PM exposure and adverse CVD events are related to acute, short-term increases in PM concentration that occur anywhere from a few hours to only a few days prior to the adverse event. Research on this topic has now shifted to studying the mechanisms underlying these epidemiological associations.
Members
Bondy, Melissa Epidemiology, UTMDACC
Delclos, George Environmental and Occupational Health , School of Public Health
Frazier, Marsha Epidemiology, UTMDACC
Li, Donghui GI Oncology & Digestive Diseases, UTMDACC
Mahabir, Somdat Epidemiology, UTMDACC
Morandi, Maria Environmental and Occupational Health , School of Public Health
Prokhorov, Alexander Behavioral sciences, UTMDACC
Spitz, Margaret Epidemiology, UTMDACC
Stock, Thomas Environmental and Occupational Health , School of Public Health
Strom, Sara Epidemiology, UTMDACC
Symanski, Elaine Environmental and Occupational Health , School of Public Health
Wu, Xifeng Epidemiology, UTMDACC
