【摘要】：目的鼻咽癌(Nasopharyngeal Carcinoma,NPC)是我國頭頸部惡性腫瘤之一,且具有較強(qiáng)的遺傳易感性。本研究選擇細(xì)胞周期依賴性激酶抑制基因(cyclin-dependent kinase inhibitor,CDKN2A),以及EB病毒感染時(shí)表達(dá)最廣泛的BamH I A區(qū)右向轉(zhuǎn)錄物家族(BamH I A Rightward Transcripts, BARTs)主要成員之一A73基因?yàn)檠芯堪悬c(diǎn),分別探討CDKN2A以及EB病毒A73基因單核苷酸多態(tài)性(Single Nucleotide Polymorphisms, SNPs)與云南鼻咽癌發(fā)病風(fēng)險(xiǎn)的關(guān)系。同時(shí)探討各基因型與鼻咽癌臨床參數(shù)之間的關(guān)系。 方法隨機(jī)抽取云南地區(qū)無血緣關(guān)系鼻咽癌患者95例和體檢中心云南籍正常對(duì)照者100例,抽提外周血基因組DNA,應(yīng)用TaqMan探針基因分型方法檢測(cè)CDKN2A基因rs1412829多態(tài)性。采用巢式PCR法及測(cè)序方法,對(duì)51例云南籍鼻咽癌患者和52例云南籍健康對(duì)照進(jìn)行EB病毒A73基因A157154C基因分型。 結(jié)果1CDKN2A基因G等位基因在NPC組和對(duì)照(NC)組中的分布頻率分別為20%和9%,兩組間比較差異有顯著性(P=0.023)。G等位基因攜帶者患NPC的風(fēng)險(xiǎn)為A等位基因攜帶者的2.497倍。(OR=2.497,95%CI=1.107～5.632,P=0.031)。 2.NPC組與NC組CDKN2A基因的AA、AG及GG的基因型頻率分布有顯著統(tǒng)計(jì)學(xué)差異(P=0.031)。 3.NPC組CDKN2A基因多態(tài)性與病理分期Ⅳ期間有相關(guān)性,即含有突變?yōu)镚等位基因較易出現(xiàn)在病程晚期的NPC患者中,差異有顯著統(tǒng)計(jì)學(xué)意義(P0.001)。 4.EB病毒基因A73基因A157154C C等位基因頻率在NPC組為96.1%,明顯高于對(duì)照組的51.9%(P0.001)；NPC組CC基因型頻率(96.1%)顯著高于對(duì)照組(42.3%),差異有顯著性(P0.001)。 5.EB病毒A73基因C等位基因攜帶者患NPC的風(fēng)險(xiǎn)為A等位基因攜帶者的22.685倍,其相對(duì)危險(xiǎn)度(OR)為22.685,95%CI=7.772～66.217,差異具有顯著統(tǒng)計(jì)學(xué)意義(P0.001)。 6.NPC組男性患者EB病毒A73基因CC基因型頻率顯著高于女性患者(73.2%vs.26.8%),差異具有顯著性(P0.001)。 結(jié)論CDKN2A基因A157154C基因多態(tài)性中G等位基因可能是NPC的危險(xiǎn)因索。該基因多態(tài)性與病理分期間存在相關(guān)性。可以認(rèn)為含有突變?yōu)镚等位基因較易出現(xiàn)在NPC病情發(fā)展的晚期,即病程的Ⅳ期。EB病毒A73基因A157154C基因多態(tài)性中CC基因型可能是NPC的危險(xiǎn)因素。該基因多態(tài)性與性別間存在相關(guān)性,在男性患者中CC基因型頻率73.2%顯著高于女性患者的頻率26.8%,這或許是NPC發(fā)病率男性顯著高于女性的原因之一。
[Abstract]:Objective Nasopharyngeal carcinoma (Nasopharyngeal Carcinoma,NPC) is one of the malignant tumors of head and neck in China and has a strong genetic susceptibility. In this study, we selected cell cycle-dependent kinase inhibitor gene (cyclin-dependent kinase inhibitor,CDKN2A) and A73 gene, one of the leading members of (BamH I A Rightward Transcripts, BARTs) family, which is the most widely expressed right-sided transcript family of BamH I A region when infected with EBV, as the target of this study. To investigate the relationship between single nucleotide polymorphism (Single Nucleotide Polymorphisms, SNPs) of CDKN2A and EB virus A73 gene and the risk of nasopharyngeal carcinoma (NPC) in Yunnan. At the same time, the relationship between genotypes and clinical parameters of nasopharyngeal carcinoma (NPC) was studied. Methods 95 unrelated nasopharyngeal carcinoma (NPC) patients and 100 normal controls were randomly selected from Yunnan province. The genomic DNA, of peripheral blood was extracted and the rs1412829 polymorphism of CDKN2A gene was detected by TaqMan probe genotyping. The A157154C gene of EB virus A73 was genotyped in 51 patients with nasopharyngeal carcinoma of Yunan nationality and 52 healthy controls by nested PCR and sequencing. Results the frequency of G allele of 1CDKN2A gene in NPC group and control group was 20% and 9%, respectively. There was a significant difference between the two groups (P < 0. 023). The risk of NPC in G allele carriers was 2.497 times higher than that in A allele carriers (OR=2.497,95%CI=1.107~5.632,P=0.031). The genotype frequencies of CDKN2A gene AA,AG and GG were significantly different between 2.NPC group and NC group (P < 0. 031). There was a significant correlation between CDKN2A gene polymorphism and pathological stage 鈪，

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