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

Ka Po Tse, Wen Hui Su, Kai Ping Chang, Ngan Ming Tsang, Chia Jung Yu, Petrus Tang, Lee Chu See, Chuen Hsueh, Min Lee Yang, Sheng Po Hao, Hong Yi Li, Ming Hsi Wang, Li Ping Liao, Lih Chyang Chen, Sheue Rong Lin, Timothy J. Jorgensen, Yu Sun Chang, Yin Yao Shugart

Research output: Contribution to journalArticle

122 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)194-203
Number of pages10
JournalAmerican journal of human genetics
Volume85
Issue number2
DOIs
StatePublished - Aug 14 2009

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Fingerprint Dive into the research topics of 'Genome-wide Association Study Reveals Multiple Nasopharyngeal Carcinoma-Associated Loci within the HLA Region at Chromosome 6p21.3'. Together they form a unique fingerprint.

  • Cite this

    Tse, K. P., Su, W. H., Chang, K. P., Tsang, N. M., Yu, C. J., Tang, P., See, L. C., Hsueh, C., Yang, M. L., Hao, S. P., Li, H. Y., Wang, M. H., Liao, L. P., Chen, L. C., Lin, S. R., Jorgensen, T. J., Chang, Y. S., & Shugart, Y. Y. (2009). Genome-wide Association Study Reveals Multiple Nasopharyngeal Carcinoma-Associated Loci within the HLA Region at Chromosome 6p21.3. American journal of human genetics, 85(2), 194-203. https://doi.org/10.1016/j.ajhg.2009.07.007