Genome-wide association study reveals multiple nasopharyngeal carcinoma-associated loci within the HLA region at chromosome 6p21.3.

Am J Hum Genet 2009 Aug 6;85(2):194-203. Epub 2009 Aug 6.

Genomic Medicine Core, Chang Gung Molecular Medicine Research Center, Chang Gung University, Taoyuan, Taiwan.

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; p(combined) = 3.9 x 10(-20) and 1.6 x 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; p(combined) = 8.97 x 10(-17)) and HLA-F (rs3129055 and rs9258122; p(combined) = 7.36 x 10(-11) and 3.33 x 10(-10), respectively). Notably, the association of rs29232 remained significant (residual p < 5 x 10(-4)) after adjustment for age, gender, and HLA-related SNPs. Furthermore, higher GABA(B) 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.

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ajhg.2009.07.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2725267PMC
August 2009
30 Reads

Publication Analysis

Top Keywords

chromosome 6p213
12
npc
9
genome-wide association
8
association study
8
hla-f rs3129055
4
rs3129055 rs9258122
4
rs9258122 pcombined
4
10-17 hla-f
4
pcombined 736
4
pcombined 897
4
gabbr1 rs29232
4
rs29232 pcombined
4
736 10-11
4
897 10-17
4
333 10-10
4
10-4 adjustment
4
residual 10-4
4
adjustment age
4
age gender
4
gender hla-related
4

Similar Publications