Use of non-steroidal anti-inflammatory drugs and risk of non-Hodgkin lymphoma: a systematic review and meta-analysis.

Epidemiological study findings regarding the association between use of non-steroidal anti-inflammatory drugs (NSAIDs) and risk of non-Hodgkin lymphoma (NHL) have been inconsistent. We aimed to systematically review epidemiological studies of the association and calculate pooled relative risks using meta-analytic methods. We searched eight electronic literature databases and three clinical trial registers to identify all studies (including observational studies and randomized clinical trials) of the association published prior to October 2013. Identified studies were independently reviewed by two researchers. We used a random effects model to calculate pooled odds ratio (PORs). Heterogeneity amongst studies was examined using Cochran's Q and I-squared (I(2)) tests; and sources of heterogeneity were explored using subgroup and meta-regression analyses. A total of 17 studies (12 case-control studies and five cohort studies), all adult studies, were included. Use of NSAIDs was not associated with overall risk of NHL [POR = 1.05, and 95% confidence interval (95% CI) 0.90-1.22] or NHL subtypes including B-cell lymphoma, T-cell lymphoma, follicular lymphoma, diffuse large B-cell lymphoma and chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). Aspirin use was associated with reduced risk of CLL/SLL (POR = 0.70, 95% CI 0.54-0.91) but not with the risk of all NHLs (POR = 1.02, 95% CI 0.89-1.17). Use of non-aspirin NSAIDs was associated with increased risk of NHL (POR = 1.41, 95% CI 1.01-1.97) amongst females only. The epidemiologic evidence remains inconclusive. Effects of NSAIDs may differ by drug type, NHL subtype, and sex and more studies taking into consideration these differences are needed.