title: Variations in the MHC region confer risk to esophageal squamous cell carcinoma on the subjects from high-incidence area in northern China.
abstract: BACKGROUND
  The human major histocompatibility complex (MHC) is the most important region in vertebrate genome, and is crucial in innate immunity. Recent studies have demonstrated the possible role of polymorphisms in the MHC region to high risk for esophageal squamous cell carcinoma (ESCC). Our previous genome-wide association study (GWAS) has indicated that the MHC region may confer important risk loci for ESCC, but without further fine mapping. The aim of this study is to further identify the risk loci in the MHC region for ESCC in Chinese population.
  
  
  METHODS
  Conditional logistic regression analysis (CLRA) was performed on 24 single nucleotide polymorphisms (SNPs) within the MHC region, which were obtained from the genetically matched 937 cases and 692 controls of Chinese Han population. The identified promising SNPs were further correlated with clinical and clinicopathology characteristics. Immunohistochemistry was performed to explore the protein expression pattern of the related genes in ESCC and neighboring normal tissues.
  
  
  RESULTS
  Of the 24 promising SNPs analyzed, we identified three independent SNPs in the MHC region associated with ESCC: rs35399661 (P = 6.07E-06, OR = 1.71, 95%CI = 1.36-2.17), rs3763338 (P = 1.62E-05, OR = 0.63, 95%CI = 0.50-0.78) and rs2844695 (P = 7.60E-05, OR = 0.74, 95%CI = 0.64-0.86). These three SNPs were located at the genes of HLA-DQA1, TRIM27, and DPCR1, respectively. Further analyses showed that rs2844695 was preferentially associated with younger ESCC cases (P = 0.009). The positive immunostaining rates both for HLA-DQA1 and TRIM27 were much higher in ESCC tissues than in neighboring normal tissues (69.4% vs. 26.8% for HLA-DQA1 and 77.6% vs. 47.8% for TRIM27, P<0.001). Furthermore, the overexpression of HLA-DQA1 is correlated significantly with age (P = 0.001) and family history (P<0.001).
  
  
  CONCLUSIONS
  This study for the first time provides evidence that multiple genetic factors within the MHC region confer risk to ESCC on the subjects from high-risk area in northern China.
authors.affiliation: Henan Key Laboratory for Esophageal Cancer Research of the First Affiliated Hospital, Zhengzhou University, Zhengzhou, Henan, China; Cancer Research Center and the Third Affiliated Hospital, Xinxiang Medical University, Xinxiang, Henan, China.
authors.forename: Fang-Fang
authors.initials: FF
authors.lastname: Shen
authors.affiliation: Henan Key Laboratory for Esophageal Cancer Research of the First Affiliated Hospital, Zhengzhou University, Zhengzhou, Henan, China.
authors.forename: Wen-Bin
authors.initials: WB
authors.lastname: Yue
authors.affiliation: Department of Thoracic Surgery, Anyang Tumor Hospital, Anyang, Henan, China.
authors.forename: Fu-You
authors.initials: FY
authors.lastname: Zhou
authors.affiliation: Cancer Research Center and the Third Affiliated Hospital, Xinxiang Medical University, Xinxiang, Henan, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Pan
authors.affiliation: Henan Key Laboratory for Esophageal Cancer Research of the First Affiliated Hospital, Zhengzhou University, Zhengzhou, Henan, China.
authors.forename: Xue-Ke
authors.initials: XK
authors.lastname: Zhao
authors.affiliation: Henan Key Laboratory for Esophageal Cancer Research of the First Affiliated Hospital, Zhengzhou University, Zhengzhou, Henan, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Jin
authors.affiliation: Henan Key Laboratory for Esophageal Cancer Research of the First Affiliated Hospital, Zhengzhou University, Zhengzhou, Henan, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Song
authors.affiliation: Henan Key Laboratory for Esophageal Cancer Research of the First Affiliated Hospital, Zhengzhou University, Zhengzhou, Henan, China.
authors.forename: Bei
authors.initials: B
authors.lastname: Li
authors.affiliation: Henan Key Laboratory for Esophageal Cancer Research of the First Affiliated Hospital, Zhengzhou University, Zhengzhou, Henan, China.
authors.forename: Xue-Na
authors.initials: XN
authors.lastname: Han
authors.affiliation: Henan Key Laboratory for Esophageal Cancer Research of the First Affiliated Hospital, Zhengzhou University, Zhengzhou, Henan, China.
authors.forename: Sa
authors.initials: S
authors.lastname: Tang
authors.affiliation: Henan Key Laboratory for Esophageal Cancer Research of the First Affiliated Hospital, Zhengzhou University, Zhengzhou, Henan, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Henan Key Laboratory for Esophageal Cancer Research of the First Affiliated Hospital, Zhengzhou University, Zhengzhou, Henan, China; Cancer Research Center and the Third Affiliated Hospital, Xinxiang Medical University, Xinxiang, Henan, China.
authors.forename: Guo
authors.initials: G
authors.lastname: Yuan
authors.affiliation: Henan Key Laboratory for Esophageal Cancer Research of the First Affiliated Hospital, Zhengzhou University, Zhengzhou, Henan, China; Cancer Research Center and the Third Affiliated Hospital, Xinxiang Medical University, Xinxiang, Henan, China.
authors.forename: Li-Sha
authors.initials: LS
authors.lastname: Chen
authors.affiliation: Henan Key Laboratory for Esophageal Cancer Research of the First Affiliated Hospital, Zhengzhou University, Zhengzhou, Henan, China; Cancer Research Center and the Third Affiliated Hospital, Xinxiang Medical University, Xinxiang, Henan, China.
authors.forename: Ya-Li
authors.initials: YL
authors.lastname: Liu
authors.affiliation: Henan Key Laboratory for Esophageal Cancer Research of the First Affiliated Hospital, Zhengzhou University, Zhengzhou, Henan, China; Cancer Research Center and the Third Affiliated Hospital, Xinxiang Medical University, Xinxiang, Henan, China.
authors.forename: Yan-Long
authors.initials: YL
authors.lastname: Hu
authors.affiliation: Cancer Research Center and the Third Affiliated Hospital, Xinxiang Medical University, Xinxiang, Henan, China.
authors.forename: Xiu-Min
authors.initials: XM
authors.lastname: Li
authors.affiliation: Department of Pathology, the Second Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
authors.forename: Jing-Li
authors.initials: JL
authors.lastname: Ren
authors.affiliation: Henan Key Laboratory for Esophageal Cancer Research of the First Affiliated Hospital, Zhengzhou University, Zhengzhou, Henan, China.
authors.forename: Li-Dong
authors.initials: LD
authors.lastname: Wang
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000453:epidemiology* / Q000235:genetics* / Q000473:pathology; D002681:China / Q000453:epidemiology; D004268:DNA-Binding Proteins / Q000235:genetics; D004938:Esophageal Neoplasms / Q000453:epidemiology* / Q000235:genetics* / Q000473:pathology; D000077277:Esophageal Squamous Cell Carcinoma; D020022:Genetic Predisposition to Disease; D060005:Genotyping Techniques; D059848:HLA-DQ alpha-Chains / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D015994:Incidence; D015810:Linkage Disequilibrium / Q000235:genetics; D016015:Logistic Models; D008285:Major Histocompatibility Complex / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011786:Quality Control; D012307:Risk Factors; D000070584:Tripartite Motif Proteins
chemical_list: D004268:DNA-Binding Proteins; D059848:HLA-DQ alpha-Chains; D009687:Nuclear Proteins; C069050:HLA-DQA1 antigen; C064419:TRIM27 protein, human; D000070584:Tripartite Motif Proteins