00000ctm a22000004a 4500 UP-1685523046125428832 Buklod 20230503092606.0 a r |||| u| ta 071031s xx d r |||| u| (iLib)UPMNL-00000056257 UPMain LG 995 2005 E6 T5 Tiangco, Beatrice Y. Markers of early biological effects after exposure to cytotoxic chemotherapeutic agents in the workplace Beatrice Y. Tiangco. 80 leaves. Thesis (Master of Science in Clinical Epidemiology)--University of the Philippines Manila. Introduction: It is unclear whether exposure to chemotherapeutic agents in the workplace increases the risk for the development of cancer. Mutations in non-disease related "reporter" genes like the hypoxanthine guanine phosphoribosyl transferase (HPRT) gene provide information regarding primary mutation frequencies, and subsequently, carcinogenicity. These mutations are of considerable value for monitoring human populations for potential health hazards due to environmental mutagens and carcinogens. Objective: To explore the exposure to cytotoxic chemotherapeutic agents as a factor in the development of early biologic markers of carcinogenesis. To assess the mutation frequency in lymphocytes using HPRT assay of tertiary oncology clinic health care workers with different degrees of exposure to cytotoxic chemotherapy and to explore if there is an association between these two variables. Study Design: Exploratory cross-sectional analytical study. Setting: UP-PGH Medical Center Cancer Institute (tertiary setting). Subject and Exposure of Interest: Health workers of UP-PGH assigned to the Cancer Institute were recruited. Sample Size: Preliminary 41 out of 169 (0.2 correlation coefficient, =0.05, = 20% Outcome Measurement: Peripheral blood from each subject was assayed using a standardized protocol for the presence of HPRT mutations. A questionnaire on the subject's age, sex, history of exposure to cytotoxic chemotherapy, illnesses, medications, family history of cancer, smoking habit, diet, alcohol intake, was used to collect pertinent data. Statistical Analysis: Descriptive statistics were used to describe subject characteristics. Associations between mutation rates and estimated exposure to chemotherapeutic agents were measured by analysis of variance. Multivariate regression analysis using SPSS was done to determine possible interaction with other epidemiological variables for frequency of HPRT mutation. Results: Forty one health workers participated in the study. The range of patient-exposure years to cytotoxic chemotherapy was 0-28,600 (mean=3115.24+4509.6). The mean frequency of variant (mutant) lymphocytes (MF) (+standard error) was 1.150 (+0.126) per million evaluable cells. Regression analysis is supported the null hypothesis that there is no difference in mutation frequency in the HPRT locus of health workers with varying degrees of exposure to cytotoxic chemotherapy in the workplace. Univariate analysis, however, showed a trend towards significance when the association between HPRT mutation in lymphocytes and age and hypertension was measured. Multivariate analysis, on the other hand, resulted in a model wherein hypertension, number of patients for whom chemotherapy is prepared on a weekly basis, and strong family history of cancer had statistically significant associations with the frequency of HPRT mutations. Conclusion: The HPRT assay, which is now locally available, can be a tool in the study of molecular epidemiology of carcinogenesis. Using regression analysis, varying degrees of exposure to chemotherapy by health workers of the UP-PGH Cancer Institute was not shown in this exploratory study to be associated with the frequency of HPRT mutation in their blood. Chemotherapy. Hypoxanthine phosphoribosyltransferase. UPMNL MED LG 995 2005 E6 T5 Thesis