Elsevier

European Journal of Cancer

Volume 42, Issue 17, November 2006, Pages 3028-3033
European Journal of Cancer

Autoimmune diseases, asthma and risk of haematological malignancies: A nationwide case-control study in Sweden

https://doi.org/10.1016/j.ejca.2006.04.021Get rights and content

Abstract

To investigate potential associations between several autoimmune diseases and haematological malignancies, we studied 39,908 cases of leukaemia, Hodgkin’s disease, non-Hodgkin’s lymphoma and myeloma that occurred during 1987–1999 in Sweden, and 149,344 controls. Hospital discharge diagnoses of psoriasis, Sjögren’s syndrome, autoimmune haemolytic anaemia, idiopathic thrombocytopenic purpura, pernicious anaemia, multiple sclerosis, rheumatic fever or asthma from 1969 to 1999 were retrieved from the Swedish Hospital Discharge Registry. Psoriasis was positively associated with leukaemia, excluding chronic lymphocytic leukaemia, (odds ratio [OR] = 1.6, 95% confidence interval [CI] 1.1–2.3) and non-Hodgkin’s lymphoma (OR = 1.6, 95% CI 1.3–2.1). Sjögren’s syndrome increased the risks of all haematological malignancies combined (OR = 4.0, 95% CI 2.3–7.0), and of non-Hodgkin’s lymphoma (OR = 6.4, 95% CI 3.5–12). These findings, together with increased risks of several haematological malignancies in autoimmune haemolytic anaemia and idiopathic thrombocytopenic purpura but not in asthma, suggest chronic autoimmunity and immune stimulation as mechanisms contributing to the development of haematological malignancies.

Introduction

The aetiology of both autoimmune diseases and haematological malignancies seems to be influenced by genetic predisposition as well as by the environment.1 A familial aggregation of autoimmune conditions, immunologic abnormalities and haematological malignancies has been observed.2, 3 This implies that conditions that alter the normal function of the immune system may not only result in an impaired ability to suppress activation of autoimmune cells, but also lead to dysfunctional elimination of malignant haematological cells.

Several studies suggest a positive association between autoimmunity and haematological malignancies. The antigenic stimulation hypothesis proposes that immune-stimulating conditions may lead to an increased risk of malignancy. The suggested mechanism involves chronic stimulation induced by activated immune cells eventually leading to random mutations in dividing cells. However, there are also some studies where no associations with haematological malignancies were found.4, 5 Contradictory to the antigenic stimulation hypothesis, most studies on asthma have reported reduced risks or risks close to unity in association with haematological malignancies.6, 7 This would be in accordance with the immune surveillance hypothesis, which proposes that allergic conditions protect against malignancies by enhancing the ability of the immune system to detect and eliminate malignant cells.8 However, in a recent study, no association between atopy and overall cancer risk was found, although among atopic men a slight excess of cases of Hodgkin’s disease (HD) was found, and among atopic women, a slight excess of non-Hodgkin’s lymphoma (NHL).9

T helper lymphocytes when activated become Th1 or Th2 effector cells identified by their production of key cytokines such as interferon-γ (Th1) and IL-4 (Th2). Th1 dominated immune responses contribute to the pathogenesis of autoimmune diseases such as psoriasis, Sjögren’s syndrome, pernicious anaemia and multiple sclerosis (MS), diseases generally regarded as T cell mediated.10 On the other hand excessive Th2 immune responses are associated with asthma, allergic conditions and autoimmune haemolytic anaemia (AIHA), idiopathic thrombocytopenic purpura (ITP) and rheumatic fever.10 These Th2 disorders are characterised by activation of B cells and the production of pathogenic immunoglobulins.

The purpose of this study was to investigate the association between chronic immune cell activation in several Th1 and Th2 mediated autoimmune diseases, asthma and the risk of developing haematological malignancies, i.e. leukaemia, HD, NHL and myeloma. We chose to study chronic immune cell activation in several immune-mediated conditions in order to address the immune surveillance hypothesis and the antigenic stimulation hypothesis concerning immune defence and carcinogenesis.

We performed a large case-control study by using data from the nationwide, population-based Swedish Hospital Discharge Registry and the Swedish Cancer Registry. By utilising high quality registries of the Swedish health care system, we had the possibility to avoid selection bias and recall bias. We obtained a larger number of exposed cases and longer periods of follow-up than most previous studies.

Section snippets

Study base and selection of cases and controls

The study base consists of the entire Swedish population during the period 1987 through 1999. All cases of haematological malignancies that occurred from 1987 to 1999 were obtained from the Swedish Cancer Registry. We identified 39,908 individuals diagnosed with haematological malignancies; 2394 cases of HD (International Classification of Diseases

Results

In Table 2, the results for leukaemia are shown, while the results for NHL, myeloma and haematological malignancies combined are presented in Table 3. Results for acute lymphoblastic leukaemia (ALL) and HD are not presented separately because the number of exposed cases with these malignancies was too few for meaningful analyses, except for individuals with asthma which is the most common of the diseases in our study.

We found increased risks of leukaemia, excluding chronic lymphocytic leukaemia

Discussion

In our material, the autoimmune diseases psoriasis, Sjögren’s syndrome, autoimmune haemolytic anaemia, and ITP were associated with increased risks for haematological malignancies, whereas no risk increases were found in association with pernicious anaemia and MS. None of the autoimmune diseases influenced the risk of myeloma. In accordance with the immune surveillance hypothesis slightly reduced risks of haematological malignancies were found in association with asthma, especially for asthma

Conflict of interest statement

None declared.

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