A CASE-REFERENT STUDY in Sweden that investigated acute myeloid leukemia and its association with electrical work, low-level gamma radiation from concrete buildings, and other agents was published previously. [1]
We now report on the continuation of that study with an expanded number of cases, i.e., 86 v. 59 included earlier. Fifty-five of the original 59 cases are included in this study.
Material and methods
Cases of acute myeloid leukemia (International Classification of Diseases 1965, ICD 205.00) diagnosed from 1977 to 1985 were collected during 1981 to 1985. The cases in the earlier study were recruited from the medical clinics of the hospitals of Linkoping, Orebro, and Umea, and from the Cytological Department of the hospital of Jonkoping. Their age ranged from 20 to 70 y. The new cases originate from only the hospitals in Linkoping and Orebro. All the cases involved were able to answer a nine-page questionnaire about different exposures, i.e., those too ill to answer the questionnaire were not included in the study. A check for completeness, achieved by comparing the number of cases of acute myeloid leukemia in the study with the number reported to the regional cancer register, revealed that one-half the number of incident cases identified during the study period were enrolled in the study.
Referents were selected from a pool of referents used in earlier studies and were selected primarily from the population register of the study area. Most referents (ages 20-80 y) of the pool were drawn randomly from the study counties. A minor group consisted of referents who were matched for age, gender, and domicile to cases who participated in the previous acute myeloid leukemia study (see introduction). Two referents per case were matched for age, gender, and county, for a total of 172 referents. This design was chosen for economic reasons and to obtain a similar geographical distribution of cases and referents inasmuch as the pool contained a disproportionate number of individuals from southern Sweden. For every case and matched referent, exposure was considered relative to year of diagnosis, i.e., 45-5 years before diagnosis, apart from radiation exposure where a time period of 25-5 years was considered.
All cases and referents in the study answered the same questionnaire (as reported in our previous publication( about chemical exposures during work and leisure time, and medical care--especially x-ray examinations and medical treatments. To account for background radiation, the questionnaire included questions about the construction material (concrete, brick, or wood)of homes and workplaces during a 20-y period (5-25 y prior to diagnosis). Exposure to background ionizing radiation from buildings was categorized into three levels (i.e., I, II, and III). It is assumed that those in the high-exposure group had an exposure that was 10-20 mSv more than that experienced by the low-exposure group.
As for x-ray examination, category 3-6 had an accumulated gamma dose between 10 and >40 mGy, and most of the subjects received 10-20 mGy to the red marrow. Category 1 received less than 1 mGy.
Statistical methods. Statistical analyses of data were based on the Mantel-Haenszel procedure [2] and the Miettinen confounder score technique. [3] The scores were obtained by multiple linear regression with the matching factors included with other variables.
[TABULAR DATA OMITTED]
Results
In the analyses of this expanded material (Table 1), a significnatly elevated risk ratio was seen for gamma radiation category III vs. I (living and working for 14 to 20 y out of a 20-y period in concrete buildings; for further details see previous study [1]). The increased risk was higher in ages 20 to 54 y, as in the previous study. Extensive x-ray examinations (categories 3-6 vs. I), and occupational exposure to gasoline (90% confidence interval, 1.1-6.5) appeared as risk factors.
Therefore, the additional cases and the new set of controls have not changed our previous result with regard to the possible role of ionizing radiation. However, some other previosly noted relationships have turned out to be less stable. Although electrical work showed increased Mantel-Haenzsel rate ratios in both studies, in the most recent study the lower bond of the 95% confidence interval no longer exceeded unity. The occupations, including electrical work, are not identical in this extended study compared with the previous one because electricians (2 cases and 9 referents) were mistakenly not included in the previous study. The inclusion of electricians would have resulted in a crude odds ratio of 2.9 (95% confidence interval 1.3-6.4).
Some of the exposures that previously appeared as risk indicators were not further analyzed in this study, either because of too few subjects being exposed (note that in this study fewer referents were used) or because the crude risk ratios were only slightly increased. Therefore, exposure to styrene, poultry contact, psychotherapeutic drugs, radiological work, and wood preservatives were not analyzed by multivariate methods.
Comment
The leukemogenic effect of category III gamma radiation is a stable finding irrespective of the two different referent series used in the previously study and in this expanded and re-evaluated study and also in the exclusive additional part of the material. Furthermore, we have not found any other exposures that would explain this relationship by confounding. It appears likely that low-level gamma radiation from buildings and medical x-rays could play a role for the induction of acute myeloid leukemia but, as is strongly indicated in the original study and in this expanded evaluation, there are other factors that probably contribute to this disorder.
References
[1] Flodin U. Fredriksson M. Persson B, Hardell L, Axelson O. Background radiation electrical work and somme other exposures associated with acute myeloid leukemia in a case referent study. Arch Environ Health 1986; 41:77-84.
[2] Mantel N, Haenszel W. Statistical aspect of analysis of data from retrospective studies of disease. J Natl Cancer Inst 1959; 23:719-48.
[3] Miettinen, OS. Stratification by a multivariate confounder score. Am J Epidemiol 1976; 104:609-20.
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