ABSTRACT: BACKGROUND:The associations between RAD51 gene polymorphisms (G135C and G172T) and risk of head and neck cancer (HNC) have been investigated, but the results are controversial. The aim of this study was to provide a more precise estimation of its relationship with HNC using a meta-analysis. METHODS:Relevant studies were retrieved from the PubMed, Excerpta Medica Database, and China National Knowledge Infrastructure. Strict selection and exclusion criteria were determined, and the odds ratio (OR) with a 95% confidence interval (CI) was used to assess the strength of the association between RAD51 polymorphisms and HNC risk. RESULTS:Six studies were eligible for RAD51 G135C (1593 cases and 1719 controls), and three studies were eligible for RAD51 G172T (997 cases and 979 controls). In the overall population, significant association between RAD51 G135C polymorphism and HNC risk was observed under allele model (C vs G: OR = 1.21, 95% CI = 1.04-1.41, P = 0.015). In the subgroup analysis by smoking status, a significant association was found among smokers (C vs G: OR = 1.59, 95% CI = 1.25-2.04; GC vs GG: OR = 2.29, 95% CI = 1.29-4.05; GC + CC vs GG: OR = 2.08, 95% CI = 1.56-2.78). When stratified based on drinking status, a significant association was found among drinkers(C vs G: OR = 1.60, 95% CI = 1.21-2.11; GC vs GG: OR = 2.50, 95% CI = 1.16-5.38; GC + CC vs GG: OR = 2.17,95% CI = 1.56-3.01). However, no significant association with HNC risk was demonstrated when stratified based on source of control and ethnicity. For G172T polymorphism, the results showed no significant risk association in overall analysis. In the subgroup analysis by ethnicity, the result suggested that a decreased HNC risk was found among Caucasians (T vs G: OR = 0.82, 95% CI = 0.72-0.95; TT vs GG: OR = 0.62, 95% CI = 0.46-0.84; TT vs GT + GG: OR = 0.64, 95% CI = 0.49-0.84). CONCLUSION:This meta-analysis suggested that RAD51 G135C is associated with increased HNC risk, especially among smokers and drinkers, while G172T polymorphism may play a protective role against HNC among Caucasians. Larger-scale and well-designed studies are needed to further clarify the association.