Grantee Research Project Results
1998 Progress Report: Molecular Biomarker of Carcinogen Exposure: 'Patched' Gene Mosaicism as a Basis for Differences in Skin Cancer Susceptibility
EPA Grant Number: R825361Title: Molecular Biomarker of Carcinogen Exposure: 'Patched' Gene Mosaicism as a Basis for Differences in Skin Cancer Susceptibility
Investigators: Brandt-Rauf, Paul
Institution: Columbia University in the City of New York
EPA Project Officer: Aja, Hayley
Project Period: November 8, 1996 through November 7, 1999
Project Period Covered by this Report: November 8, 1997 through November 7, 1998
Project Amount: $335,507
RFA: Exploratory Research - Human Health (1996) RFA Text | Recipients Lists
Research Category: Human Health
Objective:
The objective of this research is to develop a molecular biomarker for exposure to the carcinogen vinyl chloride (VC) based on the detection in serum of a particular mutant form of the ras oncogene-encoded p21 protein (Asp13p21ras). This was to be accomplished by: examining the serum expression of Asp13p21ras in cases of angiosarcoma of the liver (ASL) in VC-exposed workers where the mutational status of the tumor DNA is known in order to confirm the correlation between the biomarker in serum and tissue; and determining the serum expression in VC-exposed workers without tumors stratified by degree of VC exposure and matched unexposed controls in order to confirm the relationship between VC exposure and biomarker expression.Progress Summary:
Serum samples have been analyzed for five workers with ASL where the mutational stauts of their tumor was known, and four of the five were positive for the mutation as well as for the serum biomarker with perfect agreement between them (Li et al., 1998a). This suggests that the detection of the serum biomarker accurately reflects the occurrence of the mutation in the target tissue in exposed individuals. Serum samples from 225 VC-exposed workers and 111 age-sex-race-smoking-drinking matched unexposed controls were similarly analyzed for the serum biomarker. Overall, 76 (34%) of the VC-exposed individuals were seropositive compared to 4 (4%) of the unexposed controls, a statistically significant difference (p<0.00001). Furthermore, stratifying the exposed workers by degree of VC exposure in ppm-years by quartiles yielded a statistically significant trend for increasing odds ratio of seropositivity of the biomarker with increasing exposure (p<0.001) (Li et al., 1998b). These results suggest that this biomarker is related to VC exposure and may be an early indicator of carcinogenic risk in exposed individuals.Future Activities:
In the course of this research it has been found that another molecular biomarker for vinyl chloride exposure is likely to be the mutant protein of the p53 tumor suppressor gene. Thus, it will also be analyzed for in all of these samples to determine whether it, in combination with the Asp 13p21ras biomarker, provides additional information about exposure or risk. Furthermore, more detailed analysis of the biomarker positivity rate among the individuals in this cohort who are exposed below the current permissible exposure limit will be undertaken to explore the utility of the biomarker in risk assessment.Journal Articles on this Report : 1 Displayed | Download in RIS Format
Other project views: | All 4 publications | 4 publications in selected types | All 2 journal articles |
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Li YL, Marion MJ, Asherova M, Coulibaly D, Smith SJ, Do T, Carney WP, Brandt-Rauf PW. Mutant p21ras in vinyl chloride-exposed workers. Biomarkers 1998;3(6):433-439. |
R825361 (1998) R825361 (Final) |
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Supplemental Keywords:
RFA, Health, Scientific Discipline, Air, air toxics, Genetics, Risk Assessments, Environmental Microbiology, Molecular Biology/Genetics, cancer risk, tumor supressor genes, risk factors, intracellular expression, patched gene mosaicism, risk, risk assessment, permissible exposure levels, stratospheric ozone, dose response, carcinogens, cancer, human exposure, oncogenes, cancer risk assessment, molecular biology, monoclonal antibodyProgress and Final Reports:
Original AbstractThe perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Conclusions drawn by the principal investigators have not been reviewed by the Agency.