NM23基因多态性与胃癌遗传易感关系的研究

Correlations of Polymorphisms of NM23 with Genetic Susceptibility of Gastric Carcinoma

目的探讨中国福建地区汉族人群NM23基因NM23-1465T〉C和NM23-873C〉T单核苷酸多态与胃癌遗传易感性的关系。方法选取福建地区经组织学确诊的胃癌患者274例及年龄和性别频数匹配的对照健康体检人群283例,采用基质辅助激光解吸电离飞行时间质谱法进行NM23-1465T〉C和NM23-873C〉T多态性检测。应用非条件Logistic分析方法计算比值比（OR）及其95%可信区间（CI）,以评估不同基因型与胃癌发病风险、病理特征的关系;运用SHEsis软件进行连锁不平衡分析及单体型构建。结果 NM23-1465T〉C位点携带纯合子CC基因型的患者发生淋巴结转移的风险是携带TT＋CT基因型患者的2.5倍（OR=2.5,95%CI：0.08-2.1,P=0.029）。NM23-873C〉T的基因型分布与肿物大小、组织分化、组织浸润及淋巴结转移均未见相关性。NM23单体型与胃癌的发生无显著的相关性。结论 NM23基因多态性与胃癌的预后密切相关,NM23-1465T〉C的CC基因型有可能成为胃癌不良预后的分子指标。

Objective To explore the correlations of functional genetic variants in NM23-1465TC and NM23-873CT genes with the genetic susceptibility and gastric carcinoma（GC） in Fujian province,China.Methods Polymorphisms of NM23-1465TC and NM23-873CT in 273 gastric carcinoma patients and 283 cancer-free controls in Fujian province,frequency-matched by age and sex,were determined by Matrix-Assisted Laser Desorption/Ionization Time of Flight Mass Spectrometry（MALDI-TOF-MS）.Adjusted odds ratios（ORs） and 95% confidence evaluate the correlations of the polymorphisms with the susceptibility and gastric cancer.Linkage disequilibrium was estimated by SHEsis software.The haplotype with the existing two SNPs in NM23 gene were also constructed using SHEsis software.Results After adjustment using logistic regression for the potential confounding effects of gender and age,as compared with TT＋CT genotype,homozygous NM23-1465CC had a significantly higher risk in lymphnode metastasis with OR of 2.5,（95% CI：0.08～2.1;P=0.029）.NM23-873CT genotype was not associated with tumor size,tissue differentiation,invasion and lymph node metastasis of gastric carcinoma.No association was found between any of the NM23 haplotype and gastric cancer risk,adjusting for age and gender.Conclusions Polymorphism of NM23-1465TC is significantly related with prognosis of GC;CC of NM23-1465TC might be an indicator of lymph node in gastric cancer.