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

Wen-Hui Su,Chi-Cking Chiu,Yin Yao Shugart

doi:10.1186/s12885-015-1607-0

Abstract

BackgroundNasopharyngeal 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.MethodsWe 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.ResultsThe 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 (I2 = 47 %) that disappeared (I2 = 0 %) after stratification by moderate- and high-incidence NPC regions.ConclusionsOur 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 materialThe online version of this article (doi:10.1186/s12885-015-1607-0) contains supplementary material, which is available to authorized users.

Highlights

Nasopharyngeal carcinoma (NPC) is an epithelial malignancy highly prevalent in southern China, and incidence rates among Han Chinese people vary according to geographic region
Su et al BMC Cancer (2015) 15:598 an association between NPC and human leukocyte antigen (HLA)-A*1101, HLAA*0207, and HLA-B*5801 [7,8,9]. The distribution of these three alleles in the human genome appears to be consistent with the geographical distribution of NPC incidence in southeastern China; the allele frequency is high in regions with high NPC incidence rates [10,11,12]
Description of studies The meta-analysis was based on summary data reported by three previous Genome-wide association study (GWAS) on NPC [16,17,18] and four follow-up case–control studies [19,20,21,22] focusing on the HLA class I region

Summary

Introduction

Nasopharyngeal carcinoma (NPC) is an epithelial malignancy highly prevalent in southern China, and incidence rates among Han Chinese people vary according to geographic region. All Han Chinese populations exhibit an increased risk of NPC, the incidence rate varies by region. Su et al BMC Cancer (2015) 15:598 an association between NPC and HLA-A*1101, HLAA*0207, and HLA-B*5801 [7,8,9] The distribution of these three alleles in the human genome appears to be consistent with the geographical distribution of NPC incidence in southeastern China; the allele frequency is high in regions with high NPC incidence rates [10,11,12]. No difference in HLA allele frequency has been observed in the results of NPC association studies conducted in regions with various incidence rates [13,14,15], suggesting that the HLA genes might not directly lead to differences in NPC incidence

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Results

Conclusion