Association between Bacillus Calmette-Guerin (BCG) vaccination and lymphoma risk: A systematic review and meta-analysis.

Lymphoma etiology remains ill-defined, but immune factors seem to play a major role. The Bacillus Calmette-Guérin (BCG) vaccine, a non-specific stimulator of the cellular immune response, could influence lymphoma risk. Previous studies addressing this issue showed conflicting results. In this study, we performed a systematic review and meta-analysis to synthesize the epidemiological evidence. We conducted a systematic search of all relevant articles in PubMed, Embase, Library and Archives Canada, and Cochrane databases, up to November 1st 2018. A total of 11 studies were included. Each study was summarized, methodological quality was assessed by independent evaluators, and a consensus score was generated. Heterogeneity and publication bias were evaluated. Summary odds ratios (ORs) and 95 % confidence intervals (CIs) were estimated separately for Hodgkin's lymphoma (HL) and non-Hodgkin's lymphoma (NHL) by either a fixed effect (FE) or a random effect (RE) model depending on heterogeneity. In this meta-analysis, BCG vaccination was not associated with HL (FE summary OR = 1.10; 95 % CI 0.93-1.30), but positively associated with NHL (RE summary OR = 1.20; 95 % CI 1.01-1.43). However, when restricting to higher quality studies, no association was found between BCG vaccination and either HL (RE summary OR = 0.97; 95 % CI 0.67-1.43) or NHL (RE summary OR = 1.15; 95 % CI 0.84-1.59). Overall, our findings do not support that BCG vaccination is associated with lymphoma risk. Yet, lack of statistical power and relatively high heterogeneity among studies prevent us from making definitive conclusions. Future studies investigating this issue are needed, using robust methodology.