ReviewExcess of autoimmune and chronic inflammatory disorders in patients with lymphoma compared with all cancer patients: A cancer registry-based analysis in the south of the Netherlands
Introduction
Since the 1970s, the incidence of lymphomas has been rising in Europe and North America [1], [2], [3], subsequently levelling off in for example Sweden, Denmark and the USA since 1990 [4]. Lymphoproliferative malignancies comprise heterogeneous groups of malignancies with markedly different biological and clinical features. The exact aetiology is largely unknown for the majority of these entities, and therefore the increase in incidence is still difficult to elucidate.
Positive associations have been revealed between certain lymphomas and inflammation, autoimmune disease and infectious agents [5]. This relationship has been described in case–control studies [6], [7], cohort studies [8], reviews [9], [10], [11], and expert opinions [12]. However, considering the inherent heterogeneity and rarity among both autoimmune and chronic inflammatory disorders and lymphomas, it has been challenging to identify significant associations [11].
Infectious agents causing lymphomas can be classified according to several mechanisms. First, some viruses can directly transform lymphocytes. Second, immunodeficiency is associated with a high risk for some non-Hodgkin lymphoma (NHL) subtypes. Third, some infections increase lymphoma risk through chronic immune stimulation [13], which is also present in autoimmune diseases. Treatment of autoimmune and chronic inflammatory disorders could also affect the risk of lymphoproliferative malignancies. Another reason for the association could be shared environmental risk factors [6], and in some autoimmune diseases genetic mutations are discovered, which also lead to lymphoproliferation [14].
Co-morbidity of cancer patients is most commonly used to study treatment differences and prognostic influences [15], but co-morbidity can also be used to study its association with malignancies in a cancer registry [16] by comparing the prevalence of autoimmune and chronic inflammatory disorders among lymphoma patients with other cancer patients.
Section snippets
Study population and data collection
The Eindhoven Cancer Registry records data on all patients newly diagnosed with cancer in the southern part of the Netherlands, an area with 2.4 million inhabitants, 10 general hospitals and two large radiotherapy institutes [17]. Trained registration clerks actively collect data on patient characteristics, diagnosis, topography, histology, stage and information about initial treatment (delivered within 6 months of diagnosis) from hospital medical records. The medical record is generally regarded
Results
The prevalence of the autoimmune and chronic inflammatory disorders in the newly diagnosed cancer populations (Table 1) varied between 7.6% and 0%. The prevalence was higher for lymphomas than the other cancers, but variation between subgroups of NHL existed (Fig. 1). The details are described below.
Discussion
In general, the prevalence of autoimmune and chronic inflammatory co-morbidities was higher among newly diagnosed patients with lymphoproliferative malignancies than with the various common cancers. Especially the positive association between RA and most lymphomas, ulcers of stomach and duodenum and marginal zone lymphoma, hepatitis and diffuse large B-cell lymphoma, HIV and aggressive B-cell lymphoma, and TBC and mantle cell lymphoma was striking.
The National Institute for Public Health and
Conclusion
In conclusion, this study confirms the positive association between some autoimmune and chronic inflammatory disorders and lymphomas in a population-based cancer registry. It further explores the different effects per subgroup of lymphoproliferative malignancies. Especially the positive association between RA and most lymphomas, ulcers of stomach and duodenum and marginal zone lymphoma, hepatitis and diffuse large B-cell lymphoma, HIV and aggressive B-cell lymphoma, and TBC and mantle cell
Take-home messages
- •
There was a positive association between some autoimmune and chronic inflammatory disorders and lymphomas, and identified subtypes of haematological cancers.
- •
In our population-based cohort the association between autoimmune or chronic inflammatory disorders and lymphomas was greater as compared to other cancers.
- •
The development of lymphomas among patients with autoimmune and chronic inflammatory disorders is not unusual.
Acknowledgement
The authors thank the registration team of the Eindhoven Cancer Registry for their dedicated data collection. The study was performed with financial support from the Beunke fund at IKZ.
References (53)
- et al.
The rise in incidence of lymphomas in Europe 1985–1992
Eur J Cancer
(1999) - et al.
Autoimmune disorders and risk of non-Hodgkin lymphoma subtypes: a pooled analysis within the InterLymph Consortium
Blood
(2008) - et al.
Secondary tumours in Sjogren's syndrome
Autoimmun Rev
(2010) Autoimmune disorders and lymphoma
Ann Oncol
(2008)- et al.
The autoimmune lymphoproliferative syndrome: a rare disorder providing clues about normal tolerance
Autoimmun Rev
(2010) - et al.
Independent prognostic effect of co-morbidity in lymphoma patients: results of the population-based Eindhoven Cancer Registry
Eur J Cancer
(2005) - et al.
Hypertension as a risk factor for glioma? Evidence from a population-based study of comorbidity in glioma patients
Ann Oncol
(2004) - et al.
A comparison of the Charlson comorbidity index derived from medical record data and administrative billing data
J Clin Epidemiol
(1999) - et al.
A new method of classifying prognostic comorbidity in longitudinal studies: development and validation
J Chron Dis
(1987) - et al.
Prognostic impact of increasing age and co-morbidity in cancer patients: a population-based approach
Crit Rev Oncol Hematol
(2005)
Tumour necrosis factor antagonist therapy and cancer development: analysis of the LORHEN registry
Autoimmun Rev
Hepatitis C virus infection, mixed cryoglobulinemia and BLyS upregulation: targeting the infectious trigger, the autoimmune response, or both?
Autoimmun Rev
Autoimmunity, autoinflammation and lymphoma in combined immunodeficiency (CID)
Autoimmun Rev
The treatment of lymphoma complicating autoimmune disease: two birds with one stone?
Ann Oncol
Malignancies in systemic lupus erythematosus
Autoimmun Rev
Prevalence of HCV infection in nongastric marginal zone B-cell lymphoma of MALT
Ann Oncol
Angioedema due to acquired C1-inhibitor deficiency: a bridging condition between autoimmunity and lymphoproliferation
Autoimmun Rev
Incidence and mortality from non-Hodgkin lymphoma in Europe: the end of an epidemic?
Int J Cancer
Changing incidence of non-Hodgkin lymphomas in the United States
Cancer
Epidemiology and etiology of non-Hodgkin lymphoma—a review
Acta Oncol
Introduction: the role of inflammation, autoimmune disease and infectious agents in development of leukaemia and lymphoma
J Intern Med
Autoimmunity and susceptibility to Hodgkin lymphoma: a population-based case–control study in Scandinavia
J Natl Cancer Inst
The risk of lymphoma development in autoimmune diseases: a meta-analysis
Arch Intern Med
Autoimmune and inflammatory disorders and risk of malignant lymphomas—an update
J Intern Med
Malignant lymphomas in autoimmunity and inflammation: a review of risks, risk factors, and lymphoma characteristics
Cancer Epidemiol Biomark Prev
Infectious agents as causes of non-Hodgkin lymphoma
Cancer Epidemiol Biomarkers Prev
Cited by (23)
Lymphoma in the setting of autoimmune diseases: A review of association and mechanisms
2020, Critical Reviews in Oncology/HematologyCitation Excerpt :Although most studies support the association between RA and NHL, a study in 2008 reported no association between RA and NHL in general, except for the patients with corticosteroid and immunosuppressive drug treatments (Ekstrom Smedby et al., 2008; Baecklund et al., 2014). Another study in 2011 demonstrated that RA is associated with increased risk of most lymphoproliferative conditions but not MZL or MCL (van de Schans et al., 2011). Furthermore, a strong association between DLBCL and RA was also observed (Baecklund et al., 2014).
Advances in Inflammatory Granulomatous Skin Diseases
2019, Dermatologic ClinicsCitation Excerpt :In some instances, this dysregulation of the immune system may be triggered by, or develop as a response to, malignancy. Alternatively, it could be that chronic inflammation predisposes one to malignancy, specifically lymphoma.23 Data on this topic have been inconsistent but largely favor an increased risk of malignancy in those with sarcoidosis.
The immune landscape of myelodysplastic syndromes
2016, Critical Reviews in Oncology/HematologyCitation Excerpt :These data indirectly further confirm the increased occurrence of autoimmune manifestations in MDS patients, especially when taking into account the reduced frequency of such disorders observed in the elderly population (Vadasz et al., 2013). In our opinion, even more when considering the potential favourable prognostic impact of autoimmune manifestations, no further examinations should be routinely performed in order to explore the immunologic profile of patients newly diagnosed with MDS or idiopathic cytopenia of undetermined significance (ICUS) (van de Schans et al., 2011). Rather more focused serological or radiological testing could be driven patient by patient by specific clinical clues.
HIV/AIDS and rheumatoid arthritis
2015, Autoimmunity ReviewsCitation Excerpt :These data suggest that the occurrence of rheumatoid-like arthritis in patients with HIV/AIDS is quite rare. On the other hand, a similar study on various lymphoproliferative malignancies showed a positive association between autoimmune and chronic inflammatory disorders, suggesting either a shared etiology/pathogenesis or a direct causal relation [39]. Several antiretroviral drugs were associated with occurrence of arthralgia in clinical studies, including lamivudine, didanosine, nevirapine, tenofovir, indinavir, saquinavir, lopinavir/ritonavir, and maraviroc.
Perspectives on chronic inflammation in essential thrombocythemia, polycythemia vera, and myelofibrosis: Is chronic inflammation a trigger and driver of clonal evolution and development of accelerated atherosclerosis and second cancer?
2012, BloodCitation Excerpt :However, not until more recently, the link between inflammation and cancer has been acknowledged, being partly attributed to epidemiologic studies, which have generated data indicating chronic infections and inflammation as major risk factors for various types of cancer.38-41 Despite chronic inflammation being well described as having a major pathogenetic role in the development and progression of certain malignant lymphomas,43-45 chronic inflammation as a potential initiating event and a driver of clonal evolution in myeloid cancer has not been focused on. However, an increased risk of myeloid malignancies in autoimmune conditions has been documented46 and most recently, a large Swedish epidemiologic study concluded that chronic immune stimulation might act as a trigger for development of the myelodysplastic syndrome (MDS) and acute myelogenous leukemia (AML).47
Facts and challenges for the autoimmunologist. Lessons from the second Colombian autoimmune symposium
2012, Autoimmunity Reviews