The +252A/G polymorphism in the Lymphotoxin-α gene and the risk of non-Hodgkin lymphoma: a meta-analysis.

BACKGROUND AND OBJECTIVES Many studies have shown that the +252A/G polymorphism in the lymphotoxin-α gene is implicated in susceptibility to non-Hodgkin lymphoma but with considerable variance of results. This study aimed to clarify the overall association between the +252A/G polymorphism in the lymphotoxin-α gene and non-Hodgkin lymphoma (NHL) risk by performing a meta-analysis. MATERIALS AND METHODS The Pubmed and Embase databases were searched for all studies relating to lymphotoxin-α +252A/G gene polymorphism and NHL risk. Data were retrieved and statistical analyses were performed using the Revman 5.1 and STATA 12.0 software. RESULTS Fourteen case-control studies with 25,098 subjects were included. There was no significant association between lymphotoxin-α +252A/G gene polymorphism and the risk of NHL in the all-combined analysis (OR = 1.08, 95%CI: 0.98-1.19 for GG+GA vs. AA; OR = 1.05, 95%CI: 0.95-1.25 for GG vs. GA+AA). In a subgroup analysis by ethnicity, increased NHL risk was found in North Americans (OR = 1.21, 95%CI: 1.05-1.39 for GG+GA vs. AA), no significant association with NHL risk was identified in Asians or Europeans; In a subgroup analysis by NHL subtype, a significantly increased risk was identified in diffuse large B cell lymphoma patients (OR = 1.20 95%CI: 1.11-1.29 for GG+GA vs. AA), but not for follicular lymphoma. CONCLUSIONS This meta-analysis suggested that the lymphotoxin-α +252A/G gene polymorphism is a risk factor for NHL in North Americans, and this polymorphism may contribute to diffuse large B cell lymphoma susceptibility. Future studies that include different types of NHL and ethnicities are needed to support and extend these observations.