title: Evaluation of human leukocyte antigen-A (HLA-A), other non-HLA markers on chromosome 6p21 and risk of nasopharyngeal carcinoma.
abstract: BACKGROUND
  The association between human leukocyte antigen (HLA) genes (located in the Major Histocompatibility Complex [MHC] region of chromosome 6p21) and NPC has been known for some time. Recently, two genome-wide association studies (GWAS) conducted in Taiwan and China confirmed that the strongest evidence for NPC association was mapped to the MHC region. It is still unclear, however, whether these findings reflect direct associations with Human Leukocyte Antigen (HLA) genes and/or to other genes in this gene-rich region.
  
  
  METHODS
  To better understand genetic associations for NPC within the MHC region of chromosome 6, we conducted an evaluation that pooled two previously conducted NPC case-control studies in Taiwan (N = 591 cases and N = 521 controls). PCR-based genotyping was performed for 12 significant SNPs identified within 6p21 in the Taiwan NPC GWAS and for the HLA-A gene (exons 2 and 3).
  
  
  RESULTS
  After confirming homogeneity between the two studies, pooled odds ratios (OR) and 95% confidence intervals (CI) were estimated by logistic regression. We found that HLA-A (p-trend = 0.0006) and rs29232 (within the GABBR1 gene; p-trend = 0.005) were independent risk factors for NPC after adjustment for age, gender, study and each other. NPC risk was highest among individuals who were homozygous for the HLA-A*0207 risk allele and carriers of the rs29232 risk allele (A).
  
  
  CONCLUSIONS
  Our study suggests that most of the SNPs significantly associated with NPC from GWAS reflect previously identified HLA-A associations. An independent effect of rs29232 (GABBR1), however, remained, suggesting that additional genes within this region might be associated with NPC risk.
authors.affiliation: Genomics Research Center, Academia Sinica, Taipei, Taiwan.
authors.forename: Wan-Lun
authors.initials: WL
authors.lastname: Hsu
authors.forename: Ka-Po
authors.initials: KP
authors.lastname: Tse
authors.forename: Sharon
authors.initials: S
authors.lastname: Liang
authors.forename: Yin-Chu
authors.initials: YC
authors.lastname: Chien
authors.forename: Wen-Hui
authors.initials: WH
authors.lastname: Su
authors.forename: Kelly J
authors.initials: KJ
authors.lastname: Yu
authors.forename: Yu-Juen
authors.initials: YJ
authors.lastname: Cheng
authors.forename: Ngan-Ming
authors.initials: NM
authors.lastname: Tsang
authors.forename: Mow-Ming
authors.initials: MM
authors.lastname: Hsu
authors.forename: Kai-Ping
authors.initials: KP
authors.lastname: Chang
authors.forename: I-How
authors.initials: IH
authors.lastname: Chen
authors.forename: Tzu-I
authors.initials: TI
authors.lastname: Chen
authors.forename: Czau-Siung
authors.initials: CS
authors.lastname: Yang
authors.forename: Alisa M
authors.initials: AM
authors.lastname: Goldstein
authors.forename: Chien-Jen
authors.initials: CJ
authors.lastname: Chen
authors.forename: Yu-Sun
authors.initials: YS
authors.lastname: Chang
authors.forename: Allan
authors.initials: A
authors.lastname: Hildesheim
mesh_terms: D000483:Alleles; D002277:Carcinoma; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics*; D016001:Confidence Intervals; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D015234:HLA-A Antigens / Q000235:genetics*; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008875:Middle Aged; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000235:genetics*; D016017:Odds Ratio; D012307:Risk Factors; D013624:Taiwan
chemical_list: D005819:Genetic Markers; D015234:HLA-A Antigens