title: Heterogeneity revealed through meta-analysis might link geographical differences with nasopharyngeal carcinoma incidence in Han Chinese populations.
abstract: 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.
authors: Department of Biomedical Sciences, Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan. whsu@mail.cgu.edu.tw.|Chang Gung Molecular Medicine Research Center, Chang Gung University, Taoyuan, Taiwan. whsu@mail.cgu.edu.tw.
authors: Wen-Hui
authors: WH
authors: Su
authors: Chang Gung Molecular Medicine Research Center, Chang Gung University, Taoyuan, Taiwan. duovip@gmail.com.
authors: Chi-Cking
authors: CC
authors: Chiu
authors: Division of Intramural Research Programs, Unit on Statistical Genomics, National Institute of Mental Health, Bethesda, MD, USA. kay1yao@mail.nih.gov.|Department of Gastroenterology, Johns Hopkins Medical School, Baltimore, MD, USA. kay1yao@mail.nih.gov.
authors: Yin
authors: Y
authors: Yao Shugart
mesh_terms: D044466:Asian People; D002277:Carcinoma; D002681:China / Q000453:epidemiology; D002874:Chromosome Mapping; D002896:Chromosomes, Human, Pair 6; D018740:Genetic Heterogeneity; D020022:Genetic Predisposition to Disease; D015234:HLA-A Antigens / Q000235:genetics; D006801:Humans; D015994:Incidence; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000453:epidemiology* / Q000235:genetics*; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D017594:Publication Bias
chemical_list: D015234:HLA-A Antigens