| Abstract |
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 had 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 was 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. 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. Results for KIF5A in the worker samples showed that levels increased from 3.5 ng/ml in those cases with asbestosis that did not develop cancer to 3.9 ng/ml in those cases that did develop cancer, but this difference was not statistically significant. However, when compared to levels in normal, healthy individuals, the levels in both the workers who did not develop cancer and the workers who did develop cancer were statistically significantly elevated. Similarly, the percentages of KIF5A-positives (defined as the mean + 2SD of normals) increased from 34.2% in the workers who did not develop cancer to 48.4% in those that did, a statistically significant trend. These results remained statistically significant even after adjusting for differences in potential confounders, including asbestos exposure. Therefore, these results suggest that KIF5A levels may be a biomarker of disease progression following asbestos exposure. However, all other results, including for KIF18A, were negative or inconclusive. |
