Non-Hodgkin Lymphoma and Smoking: A Meta-Analysis of Case-Control Studies

Background: The incidence of non-Hodgkins lymphoma (NHL) has followed a sustained increasing pattern for the last few decades. Potential factors implicated in developing an increased risk for NHL include immunosuppression, bacterial, and viral infections. The pathological heterogeneity of NHL suggests multifactorial etiologies. Several reports around the world have linked lifestyle habits to the development of NHL, but thus far, the relationship between smoking and NHL has been largely inconclusive.

Objective: To perform a meta-analysis of published case-control studies to clarify the potential relationship between smoking and the development of NHL.

Methods: An English literature search was conducted using Pubmed of case-control studies investigating the relationship between smoking and development of NHL. Prospective studies, case reports, editorials and letters were not included. Data were gathered including the following variables: country of origin, source of cases and controls, number of female/male cases and controls, adjusted odds ratio (OR) with 95% confidence intervals (CI) for former and current smokers, divided by male/female when available, and adjustments. Effect measures were obtained trough fixed and random-effects models to assess for heterogeneity.

Results: Eighteen case-control studies were included in the meta-analysis. A total of 22,226 cases and 30,792 controls were finally analyzed. Based on our meta-analysis, former smokers had an OR of 1.02 (95% CI, 0.92 – 1.12) when compared to never smokers; heterogeneity between studies was evident (p < 0.001; I² = 75.3%). Current smokers, on the other hand, had an OR of 1.06 (95% CI, 1.00 – 1.14); some degree of heterogeneity was observed (p = 0.04; I² = 41.1%).

Conclusions: Despite the limitations of this meta-analysis, current smokers seem to have small but statistically significant increase in the risk of developing NHL. Clinically speaking, smoking may be a non-negligible risk factor for developing NHL. Although a causal relationship will be hard to prove, further research is needed to clarify the potential role of smoking in lymphomagenesis.