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Genome-wide Association Study Reveals Multiple Nasopharyngeal Carcinoma-Associated Loci within the HLA Region at Chromosome 6p21.3

American journal of human genetics, 2009-08, Vol.85 (2), p.194-203 [Peer Reviewed Journal]

2009 The American Society of Human Genetics ;Copyright University of Chicago, acting through its Press Aug 14, 2009 ;2009 The American Society of Human Genetics. Published by Elsevier Ltd. All right reserved.. 2009 The American Society of Human Genetics ;ISSN: 0002-9297 ;EISSN: 1537-6605 ;DOI: 10.1016/j.ajhg.2009.07.007 ;PMID: 19664746

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Title:
Genome-wide Association Study Reveals Multiple Nasopharyngeal Carcinoma-Associated Loci within the HLA Region at Chromosome 6p21.3
Author: Tse, Ka-Po ; Su, Wen-Hui ; Chang, Kai-Ping ; Tsang, Ngan-Ming ; Yu, Chia-Jung ; Tang, Petrus ; See, Lee-Chu ; Hsueh, Chuen ; Yang, Min-Lee ; Hao, Sheng-Po ; Li, Hong-Yi ; Wang, Ming-Hsi ; Liao, Li-Ping ; Chen, Lih-Chyang ; Lin, Sheue-Rong ; Jorgensen, Timothy J. ; Chang, Yu-Sun ; Shugart, Yin Yao
Subjects: Age ; Alleles ; Asian People - genetics ; Asian People - statistics & numerical data ; Biopsy ; Cancer ; Carcinogenesis ; Carcinoma - genetics ; Carcinoma - immunology ; Case-Control Studies ; chromosome 6 ; Chromosomes ; Chromosomes, Human, Pair 6 ; Cohort Studies ; Correlation analysis ; Epithelial cells ; Epstein-Barr virus ; Female ; g-Aminobutyric acid B receptors ; Gene Frequency ; Gene loci ; Genetic factors ; Genome-Wide Association Study ; Genomics ; Haplotypes ; Histocompatibility antigen HLA ; Histocompatibility Antigens Class I - genetics ; HLA Antigens - genetics ; Humans ; Immunohistochemistry ; Infection ; Linkage Disequilibrium ; Male ; Malignancy ; Nasopharyngeal carcinoma ; Nasopharyngeal Neoplasms - genetics ; Nasopharyngeal Neoplasms - immunology ; Polymorphism ; Polymorphism, Single Nucleotide ; Receptors, GABA-B - genetics ; Receptors, GABA-B - metabolism ; Single-nucleotide polymorphism ; Statistical analysis ; Taiwan ; Tumor cells
Is Part Of: American journal of human genetics, 2009-08, Vol.85 (2), p.194-203
Description: Nasopharyngeal carcinoma (NPC) is a multifactorial malignancy closely associated with genetic factors and Epstein-Barr virus infection. To identify the common genetic variants linked to NPC susceptibility, we conducted a genome-wide association study (GWAS) in 277 NPC patients and 285 healthy controls within the Taiwanese population, analyzing 480,365 single-nucleotide polymorphisms (SNPs). Twelve statistically significant SNPs were identified and mapped to chromosome 6p21.3. Associations were replicated in two independent sets of case-control samples. Two of the most significant SNPs (rs2517713 and rs2975042; pcombined = 3.9 × 10−20 and 1.6 × 10−19, respectively) were located in the HLA-A gene. Moreover, we detected significant associations between NPC and two genes: specifically, gamma aminobutyric acid b receptor 1 (GABBR1) (rs29232; pcombined = 8.97 × 10−17) and HLA-F (rs3129055 and rs9258122; pcombined = 7.36 × 10−11 and 3.33 × 10−10, respectively). Notably, the association of rs29232 remained significant (residual p < 5 × 10−4) after adjustment for age, gender, and HLA-related SNPs. Furthermore, higher GABAB receptor 1 expression levels can be found in the tumor cells in comparison to the adjacent epithelial cells (p < 0.001) in NPC biopsies, implying a biological role of GABBR1 in NPC carcinogenesis. To our knowledge, it is the first GWAS report of NPC showing that multiple loci (HLA-A, HLA-F, and GABBR1) within chromosome 6p21.3 are associated with NPC. Although some of these relationships may be attributed to linkage disequilibrium between the loci, the findings clearly provide a fresh direction for the study of NPC development.
Publisher: United States: Elsevier Inc
Language: English
Identifier: ISSN: 0002-9297
EISSN: 1537-6605
DOI: 10.1016/j.ajhg.2009.07.007
PMID: 19664746
Source: Cell Press Free Archives
GFMER Free Medical Journals
MEDLINE
PubMed Central

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Genome-wide Association Study Reveals Multiple Nasopharyngeal Carcinoma-Associated Loci within the HLA Region at Chromosome 6p21.3

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