Autoimmune and Atopic Disorders and Risk of Hodgkin Lymphoma
Autoimmune and Atopic Disorders and Risk of Hodgkin Lymphoma
Results from previous investigations have shown associations between the risk of Hodgkin lymphoma (HL) and a history of autoimmune and atopic diseases, but it remains unknown whether these associations apply to all types of HL or only to specific subtypes. We investigated immune diseases and the risk of classical HL in a population-based case-control study that included 585 patients and 3,187 controls recruited from October 1999 through August 2002. We collected information on immune diseases through telephone interviews and performed serological analyses of specific immunoglobulin E reactivity. Tumor Epstein-Barr virus (EBV) status was determined for 498 patients. Odds ratios with 95% confidence intervals were calculated using logistic regression analysis. Rheumatoid arthritis was associated with a higher risk of HL (odds ratio (OR) = 2.63; 95% confidence interval (CI): 1.47, 4.70), especially EBV-positive HL (OR = 3.18; 95% CI: 1.23, 8.17), and with mixed-cellularity HL (OR = 4.25; 95% CI: 1.66, 10.90). HL risk was higher when we used proxies of severe rheumatoid arthritis, such as ever having received daily rheumatoid arthritis medication (OR = 3.98; 95% CI: 2.08, 7.62), rheumatoid arthritis duration of 6–20 years (OR = 3.80; 95% CI: 1.72, 8.41), or ever having been hospitalized for rheumatoid arthritis (OR = 7.36; 95% CI: 2.95, 18.38). Atopic diseases were not associated with the risk of HL. EBV replication induced by chronic inflammation in patients with autoimmune diseases might explain the higher risk of EBV-positive HL.
Hodgkin lymphoma (HL), a malignant neoplasm of B-cell origin, is among the most common cancers in adolescents and young adults. Few risk factors for HL have been established. This may reflect the fact that that HL comprises at least 2 etiologically heterogeneous entities and that the composition of HL cases that are studied therefore might influence observed associations. For instance, the 20%–30% of HL cases that harbor the Epstein-Barr virus (EBV) in the malignant cells, a condition referred to as EBV-positive HL, most likely have a different etiology than the 70%–80% of cases that are EBV-negative. Thus, infectious mononucleosis, immune suppression, and cigarette smoking all seem to increase the risk of HL, particularly EBV-positive HL. Meanwhile, no etiologic factors for EBV-negative HL have been firmly established.
In several previous investigations, it has been suggested that HL risk is higher among patients with autoimmune diseases, including rheumatoid arthritis (RA), systemic lupus erythematosus, sarcoidosis, and immune thrombocytopenic purpura. Because HL EBV-status has not been available in these investigations, it is not known whether the reported associations are common to both EBV-positive and EBV-negative HL or if they are particular to one or the other. Furthermore, several autoimmune diseases have been strongly associated with a higher risk of non-Hodgkin lymphoma (NHL). Because the delineation between HL and NHL historically has been imprecise, the higher HL risk associated with autoimmune disease could theoretically reflect diagnostically misclassified cases of NHL. With one exception, none of the previous studies in which associations with autoimmune diseases were suggested included a review of tumor material to confirm the HL diagnosis.
Compared with autoimmune diseases, less attention has been paid to the putative association between risk of HL and atopic disorders. In some studies, researchers have reported a lower risk of HL in patients with asthma or hay fever; in others, there was a higher risk in patients with history of eczema; and in still others, there was no association. However, it is not known whether the reported associations with atopic disease are common to both EBV-positive and EBV-negative HL or are specific to only one, which makes it critical to know the status of the studied patients. To provide a more detailed understanding of HL epidemiology, we investigated the association between autoimmune and atopic disorders and the risk of HL by tumor EBV-status in a large Danish-Swedish case-control investigation encompassing 585 patients with classical HL and 3,187 population controls.
Abstract and Introduction
Abstract
Results from previous investigations have shown associations between the risk of Hodgkin lymphoma (HL) and a history of autoimmune and atopic diseases, but it remains unknown whether these associations apply to all types of HL or only to specific subtypes. We investigated immune diseases and the risk of classical HL in a population-based case-control study that included 585 patients and 3,187 controls recruited from October 1999 through August 2002. We collected information on immune diseases through telephone interviews and performed serological analyses of specific immunoglobulin E reactivity. Tumor Epstein-Barr virus (EBV) status was determined for 498 patients. Odds ratios with 95% confidence intervals were calculated using logistic regression analysis. Rheumatoid arthritis was associated with a higher risk of HL (odds ratio (OR) = 2.63; 95% confidence interval (CI): 1.47, 4.70), especially EBV-positive HL (OR = 3.18; 95% CI: 1.23, 8.17), and with mixed-cellularity HL (OR = 4.25; 95% CI: 1.66, 10.90). HL risk was higher when we used proxies of severe rheumatoid arthritis, such as ever having received daily rheumatoid arthritis medication (OR = 3.98; 95% CI: 2.08, 7.62), rheumatoid arthritis duration of 6–20 years (OR = 3.80; 95% CI: 1.72, 8.41), or ever having been hospitalized for rheumatoid arthritis (OR = 7.36; 95% CI: 2.95, 18.38). Atopic diseases were not associated with the risk of HL. EBV replication induced by chronic inflammation in patients with autoimmune diseases might explain the higher risk of EBV-positive HL.
Introduction
Hodgkin lymphoma (HL), a malignant neoplasm of B-cell origin, is among the most common cancers in adolescents and young adults. Few risk factors for HL have been established. This may reflect the fact that that HL comprises at least 2 etiologically heterogeneous entities and that the composition of HL cases that are studied therefore might influence observed associations. For instance, the 20%–30% of HL cases that harbor the Epstein-Barr virus (EBV) in the malignant cells, a condition referred to as EBV-positive HL, most likely have a different etiology than the 70%–80% of cases that are EBV-negative. Thus, infectious mononucleosis, immune suppression, and cigarette smoking all seem to increase the risk of HL, particularly EBV-positive HL. Meanwhile, no etiologic factors for EBV-negative HL have been firmly established.
In several previous investigations, it has been suggested that HL risk is higher among patients with autoimmune diseases, including rheumatoid arthritis (RA), systemic lupus erythematosus, sarcoidosis, and immune thrombocytopenic purpura. Because HL EBV-status has not been available in these investigations, it is not known whether the reported associations are common to both EBV-positive and EBV-negative HL or if they are particular to one or the other. Furthermore, several autoimmune diseases have been strongly associated with a higher risk of non-Hodgkin lymphoma (NHL). Because the delineation between HL and NHL historically has been imprecise, the higher HL risk associated with autoimmune disease could theoretically reflect diagnostically misclassified cases of NHL. With one exception, none of the previous studies in which associations with autoimmune diseases were suggested included a review of tumor material to confirm the HL diagnosis.
Compared with autoimmune diseases, less attention has been paid to the putative association between risk of HL and atopic disorders. In some studies, researchers have reported a lower risk of HL in patients with asthma or hay fever; in others, there was a higher risk in patients with history of eczema; and in still others, there was no association. However, it is not known whether the reported associations with atopic disease are common to both EBV-positive and EBV-negative HL or are specific to only one, which makes it critical to know the status of the studied patients. To provide a more detailed understanding of HL epidemiology, we investigated the association between autoimmune and atopic disorders and the risk of HL by tumor EBV-status in a large Danish-Swedish case-control investigation encompassing 585 patients with classical HL and 3,187 population controls.
