Identification of genes with allelic imbalance on 6p associated with nasopharyngeal carcinoma in southern Chinese.
Identification of genes with allelic imbalance on 6p associated with nasopharyngeal carcinoma in southern Chinese.
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DOI：
10.1371/journal.pone.0014562
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发表时间：
2011-01-20
期刊：
影响因子：
3.7
通讯作者：
Song YQ
中科院分区：
文献类型：
--
作者：
Li Y;Fu L;Wong AM;Fan YH;Li MX;Bei JX;Jia WH;Zeng YX;Chan D;Cheung KM;Sham P;Chua D;Guan XY;Song YQ
鼻咽癌（Nasopharyngeal carcinoma，NPC）是一种上皮源性恶性肿瘤。NPC的病因复杂，包括多种遗传和环境因素。我们采用病例对照分析的方法研究染色体6p区域与鼻咽癌的关联。共纳入360名受试者和360名健康对照者，检测了6p上的233个单核苷酸多态性（SNP）。SNPs rs 2267633（p = 4.49×10−5）、rs 2076483（最显著，p = 3.36×10−5）和rs 29230（p = 1.43×10−4）存在显著的单标记关联。 高度相关的基因是γ-氨基丁酸B受体1（GABBR 1）、人类白细胞抗原（HLA-A）和HLA复合物组9（HCG 9）。单倍型AAA（位于GABBR 1内，p值= 6.46×10−5）和TT（位于HLA-A内，p = 0.0014）存在单倍型关联。 进一步研究病例组和对照组之间的纯合子基因型频率表明，微缺失区域发生在GABBR 1和神经前体细胞表达的发育下调基因9（NEDD 9）。使用11对NPC活检样品的定量实时聚合酶链反应（qPCR）证实与邻近非肿瘤组织相比，癌组织中GABBR 1和NEDD 9 mRNA表达显著下降（p<0.05）。我们的研究表明，多个染色体6p易感基因座有助于鼻咽癌的风险，可能通过GABBR 1和NEDD 9功能丧失。
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.
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影响因子：
30.8
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