title: Identification of genes with allelic imbalance on 6p associated with nasopharyngeal carcinoma in southern Chinese.
abstract: 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.
authors.affiliation: Department of Biochemistry, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, Special Administrative Region, People's Republic of China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.forename: Li
authors.initials: L
authors.lastname: Fu
authors.forename: Alissa Michelle Go
authors.initials: AM
authors.lastname: Wong
authors.forename: Yan-Hui
authors.initials: YH
authors.lastname: Fan
authors.forename: Miao-Xin
authors.initials: MX
authors.lastname: Li
authors.forename: Jin-Xin
authors.initials: JX
authors.lastname: Bei
authors.forename: Wei-Hua
authors.initials: WH
authors.lastname: Jia
authors.forename: Yi-Xin
authors.initials: YX
authors.lastname: Zeng
authors.forename: Danny
authors.initials: D
authors.lastname: Chan
authors.forename: Kenneth M C
authors.initials: KM
authors.lastname: Cheung
authors.forename: Pak
authors.initials: P
authors.lastname: Sham
authors.forename: Daniel
authors.initials: D
authors.lastname: Chua
authors.forename: Xin-Yuan
authors.initials: XY
authors.lastname: Guan
authors.forename: You-Qiang
authors.initials: YQ
authors.lastname: Song
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D022981:Allelic Imbalance; D016022:Case-Control Studies; D002681:China / Q000453:epidemiology; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D020022:Genetic Predisposition to Disease; D006801:Humans; D009303:Nasopharyngeal Neoplasms / Q000235:genetics*; D010750:Phosphoproteins / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D018080:Receptors, GABA-B / Q000235:genetics
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C099942:NEDD9 protein, human; D010750:Phosphoproteins; D018080:Receptors, GABA-B