摘要目的 探讨中国福建地区汉族人群Nme1基因Nme1-1465 T＞C和转化生长因子(TGF)β1基因TGFβ1-509 C＞T单核苷酸多态性与胃癌遗传易感性的关系.方法 采用病例对照研究.选取福建地区组织病理学确诊的胃癌患者274例及年龄和性别频数匹配的对照健康体检人群277例,采用基质辅助激光解吸电离飞行时间质谱(MALDI-TOF-MS)方法进行Nme1-1465 T＞C(rs16949649)和TGFβ1-509 C＞T(rs1800469)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、病理特征及两基因多态性间的交互作用的关系.结果 Nme1-1465 T＞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 0.08～2.10;P=0.029).TGFβ1-509 T＞C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.肠型病例组中,经Logistic回归分析表明,与携带两个位点都是野生型纯合子Nme1 TT*TGFβ1 CC基因型的个体相比,携带位点发生变异(杂合子或突变纯合子)的Nme1 TC*TGFβ1 TC、Nme1 TC*TGFβ1TT和Nme1 CC*TGFβ1 TC基因型个体患胃癌风险分别显著降低至0.42倍(95%CI 0.54～0.94,P=0.022)、0.32倍(95%CI 0.42～0.97,P=0.013)及0.26倍(95%CI0.42～0.97,P=0.008).结论 Nme1-1465 T＞C基因多态性与胃癌的预后密切相关,同时Nme1-1465 T＞C和TGFβ1-509 T＞C在胃癌遗传易感性方面存在协同作用.

abstractsObjective To explore the correlation of functional genetic variants in Nme1-509 C＞T and TGFβ1-1465 T＞C genes to the genetic susceptibility of gastric carcinoma in Fujian province, China.Methods A case-control study was conducted in a population in Fujian province. The polymorphism of TGFβ1-509 C ＞T(rs1800469), Nme1-1465 T＞C(rs16949649) in 273 gastric carcinoma patients and 277 cancer-free controls, frequency-matched by age and sex, were analysed by using Matrix-Assisted Laser Desorption/Ionization Time of Flight Mass Spectrometry (MALDI-TOF-MS). Adjusted odds ratios (OR)and 95% confidence evaluation intervals (95% CI) measured by multivariate Logistic regression analysis were adopted in studying the correlation of the gene polymorphism with the susceptibility of gastric cancer.Results After the adjustment using Logistic regression or the potential confounding effects of gender and age, as compared with TT + CT genotype gastric carcinoma patients, the homozygous Nme1-1465CC genotype carriers had a significantly higher risk in lymph node metastasis, with the OR of 2. 5 (95% CI 0. 08-2. 10; P =0. 029). There was no association obtained between TGFβ1-509 T＞C genotype with the tumor size, cell differentiation , tumor invasion and lymph node metastasis in gastric carcinoma. In the intestinal type gastric carcinoma group , when compared with the wild homozygous Nme1 TT * TGFβ1 CC,Nme1 TC * TGFβ1 TC, Nme1 TC * TGFβ1 TT and Nme1 CC * TGFβ1 TC genotype carriers, there was a significantly decrease of risk in gastric carcinogenesis of 0. 42 fold (95% CI 0. 54-0. 94, P =0. 022), 0. 32 fold (95% CI 0.42-0.97,P =0.013) and 0.26 fold (95% CI 0.42-0.97, P =0.008), respectively.Conclusions There is a signhificant relationship between polymorphism of Nme1-1465 T＞C and the prognosis of carcinoma of stomach. It also demonstrates that coexistance of Nme1-1465 T＞C and TGFβ1-509 T＞C genes may provide a synergistic effect of increasing the susceptibility of gastric carcinogenesis.