Elsevier

Leukemia Research

Volume 25, Issue 10, October 2001, Pages 865-872
Leukemia Research

Smoking and acute myeloid leukemia: associations with morphology and karyotypic patterns and evaluation of dose–response relations

https://doi.org/10.1016/S0145-2126(01)00048-0Get rights and content

Abstract

This case-control study of tobacco smoking and acute myeloid leukemia (AML), emphasizing specific associations with morphologic and cytogenetic subtypes, comprised smoking histories for 333 cases and 351 controls. Smoking status (ever smokers versus life-long non-smokers) showed no evident effect on AML risk. However, an effect of smoking was indicated at high cumulative smoking doses (pack-years), e.g. 40 pack-years was associated with an odds ratio (OR) of 1.5 [95% confidence interval (CI) 1.0–2.3]. Among morphologic subtypes, the smoking associated OR for acute erythroleukemia was 8.9 (95% CI 1.0–76). No clear associations between smoking and cytogenetic subtypes of AML were observed.

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.

Section snippets

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.

References (44)

  • M. Crane et al.

    Correlation between selected environmental exposures and karyotype in acute myelocytic leukemia

    Cancer Epidemiol. Biomarkers Prev.

    (1996)
  • D.P. Sandler et al.

    Cigarette smoking and risk of acute leukemia: associations with morphology and cytogenetic abnormalities in bone marrow

    J. Natl. Cancer Inst.

    (1993)
  • L. Davico et al.

    Chromosome 8, occupational exposures, smoking and acute nonlymphocytic leukemias: a population-based study

    Cancer Epidemiol. Biomarkers Prev.

    (1998)
  • G.C. Kabat et al.

    Re: ‘Smoking and leukemia: evaluation of a causal hypothesis’ [letter; comment]

    Am. J. Epidemiol.

    (1994)
  • N. Mauritzson et al.

    A single-center population-based consecutive series of 1500 cytogenetically investigated adult hematologic malignancies: karyotypic features in relation to morphology, age and gender

    Eur. J. Haematol.

    (1999)
  • J.M. Bennett et al.

    Proposals for the classification of the acute leukaemias

    Br. J. Haematol.

    (1976)
  • J.M. Bennett et al.

    Criteria for the diagnosis of acute leukemia of megakaryocyte lineage (M7). A report of the French–American–British Cooperative Group

    Ann. Intern. Med.

    (1985)
  • J.M. Bennett et al.

    Proposed revised criteria for the classification of acute myeloid leukemia. A report of the French–American–British Cooperative Group

    Ann. Intern. Med.

    (1985)
  • J.M. Bennett et al.

    Criteria for the recognition of minimally differentiated acute myeloid leukaemia (AML-M0)

    Br. J. Haematol.

    (1991)
  • N. Mauritzson et al.

    Survival time in a population-based consecutive series of adult acute myeloid leukemia-the prognostic impact of karyotype during the time period 1976–1993

    Leukemia

    (1914)
  • R. Doll et al.

    Mortality in relation to smoking: 20 years' observations on male British doctors

    Br. Med. J.

    (1976)
  • Cited by (42)

    • Do the smoking intensity and duration, the years since quitting, the methodological quality and the year of publication of the studies affect the results of the meta-analysis on cigarette smoking and Acute Myeloid Leukemia AML in adults?

      2016, Critical Reviews in Oncology/Hematology
      Citation Excerpt :

      A possible reason for the association between tobacco and AML could be the presence of several leukemogenic agents, such as benzene, formaldehyde or radioactive components (polonio 210) or other carcinogens in cigarette smoking that may act through chromosomal modifications (Snyder, 2012). Several studies analyze the association between smoking and individual AML chromosomal abnormalities (Björk et al., 2001, 2009; Sandler et al., 1993; Crane et al., 1996; Moorman et al., 2002), but with contrasting results: no clear correlations with abnormalities such as -5/5q-, -7/7q-, +8 and increased associations with -7 or 7q-, -Y, +13. Nicotine comprises 1–2% of unburned tobacco, and its levels in mainstream cigarette smoke range typically from 0.5 to 2 mg/cigarette, but also several other alkaloyds structurally related to nicotine can be found in tobacco.

    • Global characteristics of childhood acute promyelocytic leukemia

      2015, Blood Reviews
      Citation Excerpt :

      Four studies [208,214,216,220] contained information about both children and adults. In addition, 10 studies [254–263] that discussed environmental and occupational related risk factors for APL in adults were included. After examining approximately 550 gathered publications, a total of 228 studies met the criteria for inclusion (Fig. 1, Table 1).

    View all citing articles on Scopus
    View full text