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Background  Nasopharyngeal carcinoma (NPC) is an epithelial malignancy highly prevalent in southern China, and incidence rates among Han Chinese people vary according to geographic region. Recently, three independent genome-wide association studies (GWASs) confirmed that  HLA-A  is the main risk gene for NPC. However, the results of studies conducted in regions with dissimilar incidence rates contradicted the claims that  HLA-A  is the sole risk gene and that the association of rs29232 is independent of the  HLA-A  effect in the chromosome 6p21.3 region.    Methods  We performed a meta-analysis, selecting five single-nucleotide polymorphisms (SNPs) in chromosome 6p21.3 mapped in three published GWASs and four case–control studies. The studies involved 8994 patients with NPC and 11,157 healthy controls, all of whom were Han Chinese.    Results  The rs2517713 SNP located downstream of HLA-A was significantly associated with NPC ( P  = 1.08 × 10 −91 , odds ratio [OR] = 0.58, 95 % confidence interval [CI] = 0.55–0.61). The rs29232 SNP exhibited a moderate level of heterogeneity (I 2  = 47 %) that disappeared (I 2  = 0 %) after stratification by moderate- and high-incidence NPC regions.    Conclusions  Our results suggested that the  HLA-A  gene is strongly associated with NPC risk. In addition, the heterogeneity revealed by the meta-analysis of rs29232 might be associated with regional differences in NPC incidence among Han Chinese people. The higher OR of rs29232 and the fact that rs29232 was independent of the  HLA-A  effect in the moderate-incidence population suggested that rs29232 might have greater relevance to NPC incidence in a moderate-incidence population than in a high-incidence population.    Electronic supplementary material  The online version of this article (doi:10.1186/s12885-015-1607-0) contains supplementary material, which is available to authorized users.

Heterogeneity revealed through meta-analysis might link geographical differences with nasopharyngeal carcinoma incidence in Han Chinese populations