Chromosome aberrations and environmental exposures in acute leukemia

Abstract

The aims of this thesis are to evaluate the role of environmental exposures, especially professional exposure to organic solvents and petroleum products in the etiology of acute leukemia and to investigate if there is a correlation between the exposure to a specific leukemogen factor and a clonal chromosome aberration of the leukemic cells.

Papers I and II present results of a case-control study of environmental exposures, in all occupations during life-time, medical treatments with medicines, chemotherapy and radiation, tobacco-use and the exposure to chemical compounds in private life in 120 patients with acute leukemia and of 120 controls, matched for age (+ 4 years), residence and sex. The patientswere treated in one of five hospitals collaborating in the Leukemia Group of Middle Sweden. The controls were taken from the population register of the taxation authorities, where all inhabitants are listed district by district. Odds ratio (OR) and multivariate analysis with logistic regression on matched data were calculated. The analyses of the chromosome aberrations were done with the Q-banding technique ad modum Caspersson. Increased risk of acute leukemia was found in painters: OR: 13; 95% confidence interval (95%CI) (binomial distribution): 2-554, (P=0.002), in all different professions exposed to organic solvents: OR: 4.9; 95%CI: 2.2-12.1, (P<0.001) and in drivers: OR: 3.0, 95%CI: 1.1-9.2 (P=0.02). Multivariate analysis showed that the significances remained, after consideration was taken to exposures to organic solvents (P<0.001), therapeutic radiation (P=0.008) and petroleum products (P=0.020). No excess risks were found after professional exposures to other nonvolatile petroleum products, as machine oil and motor oil. Thus the exposures to organic solvents and to petroleum products were independent risk-factors for AML.

Paper III describes chromosome 3 aberrations in acute myelocytic leukemia and the exposure to mutagens. All patients with monosomy 3 and deletions of chromosome 3 were found to be exposed to environmental mutagens or radiation and/or chemotherapy. They had a short survival. All breakpoints of chromosome 3 were found in the constitutional fragile site regions 3p14.2, 3q21 and 3q26-27. Dysmegakaryo-cytopoiesis was found in cases with chromosome break-points at 3q21, 3q25-29 and in monosomy 3.

Paper IV: The relationship between the occupational exposure to benzene and the occurrence of specific cytogenetic aberrations was studied in 179 patients with acute myeloid leukemia. Fifty-seven (32%) patients had a history of daily occupational exposure to benzene and 47 (82%) of these were men, 10 were women (P<0.001). Numerical chromosome aberrations (P=0.002) as well as trisomy 8 (P<0.001) were significantly more common in patients exposed to benzene compared to non-exposed. Benzene-exposure was not significantly associated with the occurrence of complex karyotypes, deletions, translocations or aberrations of chromosomes 1, 5, 7, 11, 15, 16, 17, 18 or 19. It is significantly correlated to monocytoid cell differentiation (FAB-M5).

Conclusions: The results show an increased risk of developing acute leukemia after exposure to organic solvents, especially in painters, but also in drivers and other professions exposed to organic solvents and petroleum products as gasoline and diesel. Exposure to benzene was significantly correlated with numerical chromosome aberrations, especially trisomy 8. Monocytoid cell-differentiation was significantly more often seen in benzene exposed patients than in non-exposed. Women had a significantly shorter mean-time of exposure to benzene (12.1 years), compared to men (27.8 years) (P=0.003), which could indicate a greater sensitivity to benzene exposure in women compared to men. Furthermore the results create a possibility to take preventive actions against the exposure to leukemogenic agents.