Risk of malignant lymphomas in patients with rheumatoid arthritis and in their first‐degree relatives

Abstract

Objective. Patients with rheumatoid arthritis (RA) are at increased risk for malignant lymphomas. Both conditions display a familial aggregation, and there are reports of RA and malignant lymphomas occurring in the same families. This study was undertaken to determine the risk of malignant lymphomas in first-degree relatives of RA patients, in order to investigate whether the increased risk of malignant lymphomas in RA could be due to genetic or environmental risk factors common to both conditions, rather than being a consequence of the rheumatic disease.Methods. Using Swedish nationwide and population-based registers, we identified 76,527 patients hospitalized with RA in 1964-1999 and 70,290 firstdegree relatives of a subset of these patients. These subjects were followed up for more than 3 decades, and information on cancer occurrence was recorded.Results. Patients with RA had a significantly increased risk of malignant lymphomas (535 cases; standardized incidence ratio [SIR] 2.00, 95% confidence interval [95% CI] 1.83-2.17), which was apparent for up to 2 decades of followup. Among the first-degree relatives without RA, no increased risk of malignant lymphomas was found overall, although modest and nonsignificantly elevated risk estimates were observed in subgroups. With respect to childhood cancer (0-14 years of age), we observed an increased risk of Hodgkin's lymphoma (5 cases; SIR 3.18, 95% CI 1.03-7.42).Conclusion. Patients with RA are at a markedly, but possibly time-limited, increased risk for malignant lymphomas. There is little to suggest a prominent role for coinherited or common environmental risk factors in malignant lymphomas arising in the context of RA. Instead, lymphomas complicating RA appear to be a direct consequence of the inflammation or its treatment.

Familial associations of rheumatoid arthritis with autoimmune diseases and related conditions

“…Another limitation would be that not all affected family members are hospitalized, in which case the numbers of hospitalizations would be decreased and would probably preferentially include only those patients with severe disease at presentation. In the case of RA, it has been estimated that up to 75% of Swedish patients have been hospitalized for RA at one time or another (29,30). A crude prevalence of hospitalization can be estimated by dividing the number of RA patients (47,361) by 8.5 million (the Swedish population over the study period minus the number of persons lacking family links), yielding a crude prevalence of hospitalization for RA of 0.56%; this is 80% of the assumed true population prevalence of RA (0.7%) in Sweden (31).…”

The non-Hodgkin lymphomas: A review of the epidemiologic literature

“…497 Similarly, Gridley et al 498 reported a significant positive association with RA among Swedish patients (SIR 5 1.88, 95% CI: 1.3-2.6). In a similar study with longer follow-up (for a maximum of 35 years), Ekstr€ om et al 499 estimated that RA patients had nearly twice the risk of NHL (SIR 5 1.89, 95% CI: 1.72-2.07), and additionally found that first-degree relatives of RA patients were not at significantly increased risk of NHL. The latter finding suggests that the excess risk of NHL in RA patients may be a result of the disease or its treatment, rather than shared genetic susceptibility.…”

Association of Higher Methotrexate Dose With Lymphoproliferative Disease Onset in Rheumatoid Arthritis Patients

“…Recently, MTX has been used as an anchor drug for the treatment of RA (1). However, RA patients have a high risk of onset of lymphoproliferative disease (LPD) (2). Furthermore, LPD developed by immunodeficient patients treated with MTX is defined as MTXassociated LPD (MTX-LPD) in the 2008 World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues (3).…”