19 Feb 1996: Lack of Chemical-Detoxifying Gene Produces Disease Susceptibility in Fifty Million Americans -- One in Six
Fifty million Americans are missing a gene called GSTT1 -- which appears to be responsible for detoxifying cancer-causing chemicals. These people, scientists at the National Institute of Environmental Health Sciences have now shown, are much more likely to get a serious, often fatal, bone marrow disease.
The condition, a cancer-like condition of rapid cell growth called myelodysplastic syndrome, or MDS, is not only serious in itself, it leads to a form of adult leukemia in about 30 percent of cases.
The one out of six people missing the gene do so because they inherited this gene defect from both parents. The researchers speculate that people missing the gene will prove especially susceptible to a variety of chemical-related diseases.
"This is the first disease strongly associated to the absence of this protective gene, but it certainly will not be the last," according to the principal researcher, Douglas A. Bell, PhD, of the National Institute of Environmental Health Sciences, one of the National Institutes of Health. Previously, a somewhat increased risk of developing cervical cancer had been shown in cigarette smokers also missing the gene, compared to smokers with the gene. But the cervical cancer association was not as strong as the new link to MDS.
Dr. Bell's work is part of an NIEHS effort to learn what makes some people much more susceptible to environmental chemicals.
"For example," Dr. Bell said, "while all cigarette smokers are injured, some of them develop disease at lower exposure levels or at a younger age than others.
"We are now seeing that this occurs because many people lack the ability to detoxify chemicals. While all people may be at risk, these people are at higher risk for chemical-caused cancer. If we identify these people, it might be advisable in some cases to counsel them to avoid specific occupational, environmental or life-style exposures.
"However, it is important to note that we believe it is the exposure to chemicals that drives the risk of disease -- not one's missing gene," Dr. Bell explained. "Our studies show that these gene defects have no adverse health impact in themselves among people not exposed to carcinogenic chemicals."
The linking of the bone marrow diseases called myelodysplastic syndromes or MDS to the inherited "null genotype" (as the scientists refer to individuals with missing genes from both parents) was reported in the journal The Lancet for Feb. 3, 1996.
Working with Dr. Bell at NIEHS, Research Triangle Park, NC, were Hongwei Chen, PhD, Dale P. Sandler, PhD, and Jack A. Taylor, PhD. Collaborators included Edison Liu, MD, of the University of North Carolina, Clara D. Bloomfield, MD, of Roswell Park, and David L. Shore, PhD, of Westat Inc.
Dr. Bell said his group hopes that "by identifying the most sensitive individuals in a population, we can understand the true risks posed by a given chemical exposure." Such information, he said, could improve risk assessment and attempts by various regulatory agencies to protect the public. It should also lead, he adds, to reductions in exposures to cancer-causing substances in the environment, whether natural or man-made.
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