Persistently Elevated Somatic Mutation as a Biomarker for Clinically Relevant Exposures in GWI
Abstract
It is clear that military deployment to the Gulf resulted in long-term medical effects in some personnel. The frustration has been that the symptoms have been variable and that no clear "exposure" has been found that explains either the range of symptoms shown by sufferers or the particular people who later developed these symptoms. We propose to explain the lack of a simple explanation for Gulf War illness through two observations that we have found in our studies of cancer: (1) disease is caused by the cumulative effect of many exposures rather than only one and (2) individual susceptibility to disease or exposures is as important as the exposures themselves. While working at the Lawrence Livermore National Laboratory, we developed a blood test to detect exposure to radiation, such as would occur from depleted uranium ammunition. We left Lawrence Livermore to demonstrate that the test picks up many other types of exposure, including smoking, that together cause cancer in people who lead normal lives with normal levels of exposure. Most toxic exposures result in temporary increases in the blood test, but some people, and some toxic agents, seem to continue to show the effects of exposure many years later (we showed this in a study of A-bomb survivors). In a number of studies, it is these people who continue to show effects of past exposures who are likely to develop diseases, in our studies, cancer. We suggest that Gulf War illness is caused by the combination of a number of exposures, with unique combinations resulting in unique combinations of symptoms. Our blood test is not specific to one exposure, but over lifetime measures the cumulative effects of all exposures and so is likely to identify those at greatest risk of clinical disease, including Gulf War illness. This might mean that we can identify Veterans who, despite the fact that they are not currently afflicted (or at least diagnosed) with Gulf War illness, are at greatest risk of developing the disease, so that they can be aggressively monitored and preventive measures developed and tested. The blood test is also diagnostic for babies and children with inherited diseases that make them highly susceptible to cancer. These babies and children have problems repairing the damage to their DNA that occurs just as a byproduct of living. While these babies have such low levels of DNA "repair" that they will die of cancer at a young age, many people in the normal population have less than the average repair ability, and this highly susceptible population should be counseled to avoid carcinogenic exposures. Subjects that are positive for our blood test and considered highly susceptible, both those deployed and not deployed to the Gulf, will be further tested for their DNA repair ability. By doing this, we will be able to see whether having low DNA repair was a factor in determining who would develop later illness, especially from exposures such as those in the Gulf. Again, based on our work in breast cancer, we have found a way that DNA repair can be affected by exposures and disease processes, so we will look for similar effects in subjects positive for our blood test. If this part of the study is successful, we may be able to identify those at greatest risk of developing Gulf War illness before they are even deployed.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 31, 2017
- Source ID
- W81XWH1610678
Entities
People
- Stephen G Grant
Organizations
- Nova Southeastern University
- United States Army