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Survey of Exposure to Genotoxic Agents in Primary Myelodysplastic Syndrome: Correlation with Chromosome Patterns and Data on Patients without Hematological Disease¹

Department of Medicine, Section of Hematology and Oncology, Medical College of Pennsylvania, Philadelphia, Pennsylvania 19129 [E. C. B.], Department of Social Systems Sciences, Wharton School [E. L.], and Department of Pathology and Laboratory Medicine, School of Medicine [J. M., P. C. N.], University of Pennsylvania, Philadelphia, Pennsylvania 19104

Exposure to genotoxic agents such as insecticides, pesticides, and solvents correlated with abnormal karyotypes and development of acute nonlymphocytic leukemia (ANLL) similar to, but to a lesser degree compared to, patients exposed to irradiation and alkylating drugs in several reports. Because of the natural progression of myelodysplastic syndrome (MDS) to ANLL, we investigated the relationship of exposure to these carcinogens in patients with primary MDS by having 52 such patients diagnosed and referred to our center answer an occupational/environmental questionnaire. We excluded all secondary MDS patients with exposure to previous chemotherapy and radiation for a previous malignancy. In addition, we prospectively gave the same questionnaire to a similar number of age- and sex-matched comparable control patients from the same socioeconomic group based on their residence, health insurance coverage, and occupation.

We found a 46% exposure rate to implicated genotoxic agents in our patients with MDS. Patients with MDS who were exposed had 75% incidence of a poor prognosis French-American-British classification compared to 57% in the nonexposed group but the difference was not significant (P = 0.089). However, the karyotypic abnormalities that were associated with exposure in ANLL were found equally in both exposed (55%) and nonexposed groups (50%) of our MDS patients and our control group had a similarly high exposure rate at 40% to genotoxins.

Implicating a relationship between exposure to pesticides and solvents in ANLL and MDS is difficult. All the previous studies indicating such a relationship did not use a control group of patients. Our findings indicate the pitfalls of historical data without investigating the bias of obtaining an exposure history. However, our findings that the majority of our MDS patients came from the middle socioeconomic group which has a high exposure rate as shown by our control group indicate a relationship and that prospective follow-up of the exposed cohort of control patients should be done to determine if ANLL and MDS will increase after a latent period compared to the nonexposed controls.

¹ Supported by Grant CA 42232, USP14S and the Hematology/Oncology Research Fund of the Medical College of Pennsylvania.

² Present address: Department of Internal Medicine, Duke University Medical Center, Durham, NC.

³ To whom requests for reprints should be addressed, at Department of Medicine, Section of Hematology/Oncology, Medical College of Pennsylvania, 3300 Henry Avenue, Philadelphia, PA 19129.

Received 10/19/89. Accepted 7/17/90.