Cancer Research Institute, Central South University, 410078 Changsha, People's Republic of China.
Med Oncol. 2012 Sep;29(3):1456-62. doi: 10.1007/s12032-011-0079-6. Epub 2011 Oct 20.
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, χ(2) = 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, χ(2) = 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.
乳铁传递蛋白(LTF)是非特异性免疫系统的组成部分,具有抗细菌、真菌和多种病毒的抗菌特性。LTF 的基因编码是多态的,在普通人群中存在几种常见的等位基因。我们之前的研究发现,LTF 抑制鼻咽癌细胞(NPC)的体外和体内增殖。为了更好地理解 LTF 介导的 NPC 细胞抗肿瘤活性的一种可能机制,本研究我们调查了 NPC 中 LTF 基因多态性(rs1126477、rs1126478、rs2073495 和 rs9110)的分布,并揭示了这些多态性是否与 LTF 基因表达相关。结果发现,rs2073495 和 rs9110 与 NPC 显著相关。与对照组相比,NPC 患者中 CC 基因型的频率更高,GG 或 TT 基因型的频率更低(P<0.05,χ(2)分别为 8.73 和 9.33)。CC 基因型是 NPC 的危险因素。单体型分析表明,与对照组相比,NPC 患者中 'A-G-G-T' 单体型(由 rs1126477、rs1126478、rs2073495 和 rs9110 构建)的频率较低(P=4.12×10(-6) <0.001,χ(2)=21.25)。具有 'A-G-G-T' 单体型的人群患 NPC 的风险为 0.322 倍。与没有 'A-G-G-T' 单体型的 NPC 组织和对照组织相比,LTF 基因在 NPC 组织和对照组织中的表达较高。这些发现表明 rs2073495 和 rs9110 可能在 NPC 生理过程中发挥重要作用。