Background and objective: The transport of nucleoside transmembrane mediated by equilibrative nucleoside transporter (ENT) plays an important role in regulating various cellular functions, and the ENT gene may be candidate gene of tumors. The aim of this study is to investigate the association between the single nudcleotide polymorphism (SNP) of ENT3 and the hereditary susceptibility of lung cancer.
Methods: A case-control study was performed involved in 351 lung cancer patients and 207 cancer-free controls from Chinese population in Shanghai pulmonary hospital. The rs10999776 (C>T) polymorphism was determined by using Real-time PCR with AllGlo probes. The frequency distribution of genotypes and allele between lung cancer and controls groups was analyzed by chi-square test. The association between polymorphism in the ENT3 gene with the risk of lung cancer was estimated by computing odds ration (OR) and 95%CI.
Results: The genotype (CC, TC, IT) and allele distribution of the ENT3 SNP in the patients with lung cancer was not significantly different compared with that in controls (P > 0.05). Compared with never-smokers with wild homozygous genotype, smokers with T allele (TC+TT) had increased risk of lung cancer (OR = 2.848, 95% CI: 1.536-4.879, P = 0.005), and those with pack-years of smoking more than 30 had higher risk (OR = 3.076, 95% CI: 2.308-6.741, P = 0.001). And the risk of squamous cell carcinoma significantly increased in smokers, especially those with T allele (TC+TI) genotype (OR = 6.066, 95% CI: 2.884-12.758, P < 0.001). The genotype with smoking conditions had no significant effect on adenocarcinoma (all P > 0.05).
Conclusion: The results suggested rs10999776 polymorphism may implicate in the risk of squamous cell carcinoma in Chinese population which may interact with smoking-exposure.
背景与目的: 核苷转运蛋白介导的核苷跨膜转运在调节细胞功能中发挥重要作用，可能是某些肿瘤的候选易感基因。本研究旨在探讨核苷转运蛋白基因ENT3单核苷酸多态性与肺癌易感性的关系。
方法: 采用病例对照研究，收集2008年5月-2009年5月于上海市肺科医院就诊的原发性肺癌患者351例和同期住院的非肿瘤患者207例，应用AllGloTM探针结合实时荧光PCR方法分析肺癌组和对照组ENT3基因rs10999776多态位点的基因型分布情况，比较不同基因型与肺癌易感性的关系以及不同基因型联合吸烟对肺癌易感性的影响。肺癌组与对照组基因型和等位基因分布比较用χ2检验，以调整比值比及95%CI表示相对危险度，所有统计检验均为双侧概率检验，所有资料均用SPSS软件进行统计。
结果: 肺癌患者rs10999776多态位点的CC、TC、TT基因型和C、T等位基因频率分布与对照组比较无统计学差异（P > 0.05）。与非吸烟的野生型纯合子个体比较，携带突变等位基因T（TC+TT）的吸烟个体罹患肺癌的风险性明显增加，且吸烟≥30包/年者风险性更高，调整OR值分别为2.848（95%CI: 1.536-4.879, P=0.005）、3.076（95%CI: 2.308-6.741, P=0.001）。而对肺癌不同组织类型的分析发现，三种基因型的吸烟个体罹患肺鳞癌的风险性均增加，且携带突变等位基因T的个体风险性更高，调整OR值为6.066（95%CI: 2.884-12.758, P < 0.001）。而rs10999776（C＞T）多态性联合吸烟对肺腺癌则无显著影响。
结论: 核苷转运蛋白基因ENT3 rs10999776多态性可能与肺鳞癌的发病风险相关，且与吸烟环境暴露存在一定的相互作用。