The goal of this research is two fold: to identify genes involved in cancer susceptibility and to characterize the pattern of genetic damage caused by different environmental agents. On the former we have publications in press showing increased risk of hepatocellular carcinoma for persons carrying a variant allele of the L-myc proto-oncogene, increased risk of bladder cancer for persons who have inherited defective copies of glutatione-S-transferase M1 gene, and reported a new variant of the N-acetyltransferase gene which is common in African-Americans but not in caucasians. In addition we have published descriptive work on the carcinogen metabolism genes CYP1A1 and CYP1A2, along with two statistical papers on methods of assessing genetic susceptibility and testing for gene-environment interaction. On the latter goal we have published a paper showing that ras oncogene activation is strongly linked to occupational and chemical exposure in acute myeloid leukemia. In addition we have recently completed a study describing unique mutations in the tumor suppressor gene p53 in radon-exposed uranium miners. Future plans include completing analysis for a variety of susceptibility genes in relation to risk of bladder cancer and testing associations between specific occupational or environmentally induced bladder and lung cancer and defects in oncogenes and tumor suppressor genes.

National Institute of Health (NIH)
National Institute of Environmental Health Sciences (NIEHS)
Intramural Research (Z01)
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