Novel Biomarkers of Asbestos Carcinogenesis

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DESCRIPTION (provided by applicant): NIOSH recognizes the need for research for the development of methods for measuring the early markers of adverse health effects from workplace exposures. This is especially important for asbestos-related cancers because asbestos remains a major occupational health risk in several of the industries targeted in the National Occupational Research Agenda's Sectors Program, such as construction, manufacturing, mining, and transportation and utilities, and cancer remains a major disease category of concern in the NIOSH Cross- Sector Program; world-wide, it is estimated that more than a hundred thousand workers die each year from asbestos-related diseases, particularly cancer. In preliminary studies based on the proteomic analysis of a limited number of banked serum samples from a cohort of asbestosis cases, we have tentatively identified novel kinesin family protein biomarkers (KIF5A and KIF18A) that may be highly correlated with the subsequent development of cancer in these workers. The purpose of this proposal is to follow up on this finding in a systematic and quantitative fashion by using enzyme-linked immunosorbent assays (ELISAs) to analyze all of the 364 serum samples from all of the 110 workers in this cohort for levels of KIF5A and KIF18A. These levels will be correlated with the subsequent development of cancer in these workers. In addition, tumor tissue samples are available from some of the resultant tumors which will be quantitatively analyzed by immunohistochemistry for the levels of expression of KIF5A and KIF18A, and the serum levels of these biomarkers will be correlated with the levels of expression in the tumors. This research would be the first systematic study of kinesin proteins as potential serum biomarkers for cancer, and, if successful, would demonstrate that these kinesin biomarkers could be useful for identifying those individuals with asbestosis who are at the highest risk for developing cancer and who could then be selected for more aggressive and targeted preventive/therapeutic interventions, thus reducing the burden of asbestos-related malignancies. PUBLIC HEALTH RELEVANCE: This research has significant Public Health Relevance because hundreds of thousands of workers in the U.S. have been exposed to asbestos and are at risk for asbestos-related malignancies. The goal of this research is to develop potential new biomarkers for cancer risk in these workers. These biomarkers could then be used to identify those asbestos-exposed workers at the highest risk for cancer so that they could be targeted with interventions for prevention or early treatment to reduce the burden of cancer deaths and disability from asbestos exposures.