Risk of nasopharyngeal carcinoma associated with polymorphic lactotransferrin haplotypes
Risk of nasopharyngeal carcinoma associated with polymorphic lactotransferrin haplotypes
复制标题
与多态性乳转铁蛋白单倍型相关的鼻咽癌风险
DOI：
10.1007/s12032-011-0079-6
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发表时间：
2012-09-01
期刊：
影响因子：
3.4
通讯作者：
Li, Guiyuan
中科院分区：
文献类型：
--
作者：
Zhou, Yanhong;Wang, Wei;Li, Guiyuan
乳铁蛋白（LTF）是非特异性免疫系统的一个组成部分，对细菌、真菌和多种病毒具有抗菌特性。编码LTF的基因具有多态性，在普通人群中存在几种常见的等位基因。我们先前的研究发现，乳铁蛋白在体外和体内都能抑制鼻咽癌（NPC）细胞的增殖。为了更好地理解乳铁蛋白介导的抗鼻咽癌细胞活性的一种可能机制，在本研究中，我们调查了乳铁蛋白基因多态性（rs1126477、rs1126478、rs2073495和rs9110）在鼻咽癌中的分布情况，并揭示了这些多态性是否与乳铁蛋白基因表达相关。研究发现，rs2073495和rs9110与鼻咽癌显著相关。与对照组相比，鼻咽癌患者中CC基因型频率较高，GG或TT基因型频率较低（分别为P < 0.05，χ² = 8.73和9.33）。CC基因型是鼻咽癌的危险因素。单倍型分析表明，与对照组相比，鼻咽癌患者“A - G - G - T”单倍型（由rs1126477、rs1126478、rs2073495和rs9110构建）的比率较低（P = 4.12×10⁻⁶ < 0.001，χ² = 21.25）。具有“A - G - G - T”单倍型的人群患鼻咽癌的风险是0.322倍。在具有“A - G - G - T”单倍型的鼻咽癌组织和对照组织中，乳铁蛋白基因的表达较高。这些研究结果表明，rs2073495和rs9110在鼻咽癌的生理过程中可能起重要作用。
Lactotransferrin (LTF) is a component of the nonspecific immune system, having antimicrobial properties against bacteria, fungi, and several viruses. The gene coding for LTF is polymorphic, with the occurrence of several common alleles in the general population. Our previous study found that LTF inhibited nasopharyngeal carcinoma (NPC) cell proliferation in vitro and in vivo. To better understand one possible mechanism of LTF-mediated antitumor activity in NPC cells, in the present study, we investigated the distribution of LTF gene polymorphisms (rs1126477, rs1126478, rs2073495, and rs9110) in NPC and revealed whether these polymorphisms were associated with LTF gene expression. It was found that rs2073495 and rs9110 were correlated significantly with NPC. The frequency of CC genotype was higher and GG or TT genotype was lower, in NPC patients compared with that in the control group (P< 0.05, χ2= 8.73 and 9.33, respectively). CC genotype is the risk factor for NPC. Haplotype analyses indicated that NPC patients had lower rate of ‘A-G-G-T’ haplotype (constructed with rs1126477, rs1126478, rs2073495, and rs9110) compared with controls (P= 4.12 × 10−6< 0.001, χ2= 21.25). The population with ‘A-G-G-T’ haplotype had 0.322-fold risk to be NPC. The expression of LTF gene was high in NPC tissues and control tissues with ‘A-G-G-T’ haplotype compared with these without its. These findings suggested that rs2073495 and rs9110 could play important roles in NPC physiological processes.