Genetics of Susceptibility and Risk Research

Rats have been employed in both small-scale and large-scale studies that lead to insights on the genetics of susceptibility, and in assessment of risks to human health.  The National Institute of Environmental Health Sciences (NIEHS) manages a Center for Rodent Genomics to meet their goals of effectively using animal model resources to investigate environmental assaults that could lead to unwanted changes in humans.  Coordination with the National Toxicology Program (NTP) efforts to apply the tools of modern toxicology and molecular biology to evaluating chemical exposures will provide benefits to the public health, and a great deal of information can be obtained from the NTP studies, which can be mined for useful conclusions on comparative susceptibilities.  Another project called ToxCast from the Environmental Protection Agency also explores risks from environmental exposures with both computer modeling and rat in vivo data, and is yielding new understanding of the underlying responses to chemicals.  Increasingly the tools of genomics will offer leads for susceptibility, toxicity and prevention, using rodents as a model.

An early model that demonstrated heritability of a predisposition to cancer was the Eker model of renal carcinoma in rats. Insights on the development of prostate cancer have been provided by inbred rat models. Genetic predisposition to hepatocellular carcinoma is being pursued in rodents. Resistance to the development of this cancer can also offer crucial knowledge.  These studies are yielding important clues to the mechanisms of this cancer.

Another cancer amenable to research in rat models is that of mammary cancer. Rats susceptible to mammary cancer are widely studied.  Various rat models are offering leads on the important pathways in this disease. Comparative genetics in this system will help to tell us more about human cancers, and about the fidelity of the models. 

Understanding the responses of models to carcinogenic challenges informs us about many important aspects of risk.  Some of these may be exposures such as food contaminants, dietary supplements, chemical or organic pesticides, or other environmental exposures such as arsenic or asbestosComparing different types of exposures will also aid in our understanding of environmental risks.