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Nasopharyngeal carcinoma (NPC) is a malignancy of epithelial origin. The etiology of NPC is complex and includes multiple genetic and environmental factors. We employed case-control analysis to study the association of chromosome 6p regions with NPC. In total, 360 subjects and 360 healthy controls were included, and 233 single nucleotide polymorphisms (SNPs) on 6p were examined. Significant single-marker associations were found for SNPs rs2267633 (p = 4.49×10 −5 ), rs2076483 (most significant, p = 3.36×10 −5 ), and rs29230 (p = 1.43×10 −4 ). The highly associated genes were the gamma-amino butyric acid B receptor 1 ( GABBR1 ), human leukocyte antigen ( HLA-A ), and  HLA  complex group 9 ( HCG9 ). Haplotypic associations were found for haplotypes AAA (located within  GABBR1 , p-value  = 6.46×10 −5 ) and TT (located within  HLA-A , p = 0.0014). Further investigation of the homozygous genotype frequencies between cases and controls suggested that micro-deletion regions occur in  GABBR1  and neural precursor cell expressed developmentally down-regulated 9 ( NEDD9 ). Quantitative real-time polymerase chain reaction (qPCR) using 11 pairs of NPC biopsy samples confirmed the significant decline in  GABBR1  and  NEDD9  mRNA expression in the cancer tissues compared to the adjacent non-tumor tissue (p<0.05). Our study demonstrates that multiple chromosome 6p susceptibility loci contribute to the risk of NPC, possibly though  GABBR1  and  NEDD9  loss of function.

Identification of Genes with Allelic Imbalance on 6p Associated with Nasopharyngeal Carcinoma in Southern Chinese