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Thursday, August 27, 1998, 12:00 p.m. EDT
Some smokers face a particularly high risk of bladder cancer because of variations in two genes that work together to escalate their already high risk, scientists at the National Institute of Environmental Health Sciences report.
The distinctive study may be the first to define a three-way gene-gene-environmental relationship to disease risk.
Both genes were previously known to have roles in metabolizing a chemical, arylamine, present in tobacco smoke and some occupations, such as those involving petroleum. But surprisingly, while a variation of one of the genes (NAT1) alone increased risk about twofold for smokers, variations of the second gene (NAT2) conveys no demonstrated risk unless the NAT1 variation is also present. When both variations are present, the risk for smokers is highest.
For example, someone who smokes 25 years and carries the at-risk copies of both genes has a tenfold higher risk of bladder cancer than someone who does not smoke.
The study, conducted among bladder cancer patients at the nearby Duke University Medical Center, Durham, N.C., and the University of North Carolina Hospitals, Chapel Hill, is reported in the journal Cancer Research, Vol. 58, issue 15. NIEHS is in Research Triangle Park, N.C.
"While everyone who smokes experiences higher risks of bladder cancer, this study suggests there may be small, genetically defined subgroups that suffer much higher risks than the general population," Dr. Taylor said. Though this is a preliminary study, the authors point out that people known to be in the higher risk subgroups could avoid smoking to decrease their risk of bladder cancer.
The authors are Jack A. Taylor, M.D., Ph.D., David M. Umbach, Ph.D., Douglas A. Bell, Ph.D. Elizabeth Stephens, and Trisha Castranio, all of NIEHS, and Cary Robertson, M.D. and David Paulson, M.D. of the department of surgery at Duke, and James Mohler, M.D. of the department of surgery at UNC.
About the National Institute of Environmental Health Sciences (NIEHS): NIEHS supports research to understand the effects of the environment on human health and is part of the National Institutes of Health. For more information on NIEHS or environmental health topics, visit www.niehs.nih.gov or subscribe to a news list.
About the National Institutes of Health (NIH): NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.
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