胃癌患者肿瘤坏死因子基因型与其血清水平的关系

The relationship between tumor necrosis factor gene polymorphisms and its serum level in gastric cancer patients

目的研究胃癌患者肿瘤坏死因子（TNF）-a308和TNF-a252基因型与血清TNF—a、β水平的关系。方法收集病理诊断证实的57例胃癌患者，49例来自武汉大学中南医院，8例来自湖北省肿瘤医院。同时选取年龄与性别相匹配的18名健康体检者作为对照。采用限制性片段长度多态性聚合酶链反应（PCR—RFLP）方法检测患者外周静脉血。采用ELISA方法检测57例胃癌患者及18名对照者的血清TNF—a、D水平，比较胃癌患者各TNF基因型之间血清TNF水平的差异及其与对照者血清TNF水平的差异。分析胃癌患者TNF水平与临床病理特征的关系。结果胃癌患者总体血清TNF—a水平较对照组明显增高（中位数445×10^-3ug／L比5×10^-3ug／L，P〈0．05），而且TNF—a308和TNF-β252各基因型（TNF-a308GA基因型6例、GG基因型51例，TNF—β252GG基因型17例，GA和AA基因型各20例）的血清TNF-a水平较对照组也明显增高（P〈0．05），但血清总体TNF—β水平与对照组比较差异无统计学意义（P〉0．05）。此外，TNF—a308G／TNF-β252G和TNF-a308G／TNF-β252A单倍型胃癌患者血清TNF—a水平较对照组也明显增高（P〈0．05），其增高与血清总体TNF-a水平一样，与患者年龄、淋巴结转移显著相关（P〈0．05）。TNF—a308A和TNF-β252G的高危等位基因携带者的TNF-β水平与吸烟史显著相关（P〈0．05）。结论胃癌患者血清TNRa水平增高与TNF-a308和TNF-β252基因型无显著相关性。TNF—a308G／TNF-β252G和TNF—a308G／TNF-β252A单倍型胃癌患者的血清TNF-a水平增高与年龄、淋巴结转移显著相关，提示TNF基因单倍型对胃癌TNF的表达及临床类型可能具有一定的影响。

Objective To investigate the relationship between tumor necrosis factor （TNF）- a308, TNF-β3252 genotypes and serum TNF-a and TNF-β levels in patients with gastric cancer （GC）. Methods A total of 57 pathological diagnosed GC patients were collected, of which 49 cases were from Zhongnan Hospital of Wuhan University and 8 cases were from Tumor Hospital of Hubei Province. Another 18 age and sex matched healthy controls were enrolled at the same time. The TNF-a308 and TNF-β252 polymorphism was genotyped by polymerase chain reaction-restriction fragment length polymorphism （PCR-RFLP）. The serum TNF-a and TNF-β levels of 57 GC patients and 18 healthy controls were measured by ELISA. The difference of TNF serum level in different TNF genotypes of GC and the difference between GC patients and the healthy controls was analyzed. Its relationship with clinical pathological characters was also analyzed. Results With TNF-a308 genotype, GA were 6 cases and GG were 51 cases. With TNF-β252 genotype, GG were 17 cases, GA and AA each were 20 cases. The serum TNF-a level of GC patients was significant higher than that of healthy controls （median 445×10^-3 ug/L vs 5 × 10^-3 ug/L, P〈0. 05）, and the serum level of each TNF-a308 and TNF-β 252 genotypes was significant higher than that of healthy controls （P〈0.05）. However there was no statistical significance in TNF-β level compared with healthy controls （P〈0.05）. In addition, the serum TNF-a levels of the TNF-a308G/TNF-β252G and TNF-a308G/TNF-β252A haplotypes in GC patients were significant higher than those of the healthy controls （P%0.05）, and the increase like serum TNF-a level was associated with the patients＇age and lymph node metastasis （P〈0.05）. The TNF-β level in patients with TNF-a308A and TNF-β252G high-risk haplotypes showed a significant relation with smoking history （P〈 0. 05）. Conclusions Serum TNF-a level of GC patients was significantly higher, however there was no significant association between the increase and TNF-a308 and TNF-β252 genotypes. The serum TNF-a levels of TNF-a308G/TNF-β252G and TNF-a308G/ TNF-β252A haplotypes in GC patients were significant higher, and associated with the patientsrage and lymph node metastasis. It was indicated that TNF haplotypes may have certain impact on the TNF expression and clinical subtypes in GC.