Smoking and acute myeloid leukemia: associations with morphology and karyotypic patterns and evaluation of dose–response relations
Introduction
Tobacco smoking is generally recognized as a weak risk factor for myeloid malignant disorders [1], [2], [3], [4]. For acute myeloid leukemia (AML), a meta-analysis has indicated a 30% elevated risk among ever smokers compared to life-long non-smokers [2]. However, the strength of the association between smoking and AML may vary between different morphologic or cytogenetic subtypes and may be dependent on quantitative smoking behavior. Based on experimental data, it has been hypothesized that certain etiologic agents may induce tumors with characteristic clonal chromosomal aberrations (CCA) [5], [6]. Studies of CCA in AML secondary to chemotherapy have provided support for this hypothesis [7], [8], [9]. However, only a few studies of AML and smoking have analyzed associations with morphology or CCA [8], [10], [11]. Dose–response relations between smoking and AML have been studied more extensively but have yielded inconsistent results [12].
The aim of this study of AML and tobacco smoking was threefold: (1) to investigate risk differentiation with respect to morphology, (2) to explore the role of CCA as markers of a specific genotoxic exposure, and (3) to evaluate dose–response relations.
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Cases series
The study, approved by the Ethics Committee of Lund University, is based on 372 adult AML patients from Southern Sweden, cytogenetically analyzed during 1976–1993 at the Department of Clinical Genetics, Lund, Sweden. The department performs cytogenetic investigations on suspect AML from the catchment areas of Lund University Hospital, as well as from other parts of Southern Sweden. All referrals for cytogenetic investigations are made within the public health system. In the catchment areas of
Qualitative smoking information
The prevalence of ever smokers and the median pack-years were somewhat higher among cases than among controls (Table 1). The risk estimate for all AML for ever smokers versus life-long non-smokers showed no clear effect (OR 1.2; 95% confidence interval (CI) 0.87–1.7). This estimate did not change when subjects with a history of chemotherapy or radiotherapy were excluded (OR 1.2; 95% CI 0.89–1.7). Further analyses are only presented for de-novo AML. Restricting the analyses to smoking behavior
Discussion
Our risk estimate for AML overall for ever smokers versus life-long non-smokers was consistent with results from a meta-analysis, based on seven case-control studies [2], as well as with results from a recent study of acute leukemias [27]. Negative findings, but with no separate effect estimates for AML, were recently reported in a large study of smoking and myeloid malignant disorders [28]. Not all studies of smoking and AML have shown evidence of a dose–response relation [29], [30]. We
Acknowledgements
Siv Nilsson, Siv Hansson, and Ingegärd Nilsson performed the interviews. Gudrun Persson and Ulrika Wallin were responsible for interview administration and data entry. Asta Persson and Gunnel Nilsson retrieved the medical records. Valuable contributions were also made by Håkan Tinnerberg. The project was supported by grants from the Swedish Council for Work Life Research, the Swedish Cancer Society, and the Medical Faculty of Lund University.
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