探讨胃癌患者肿瘤坏死因子α基因启动子308位点(TNF-α-308)多态性与血清胃蛋白酶原(pepsinogen, PG)的相关性。

用聚合酶链反应-限制性片段长度多态性技术测定500例胃癌患者(胃癌组)和500名健康体检者(健康对照组)TNF-α-308基因型，同时检测其TNF-α和血清PG亚群(PGⅠ和PGⅡ)水平，分析TNF-α-308多态性与血清PG水平的关系。

胃癌组TNF-α-308的GG、GA、AA基因型和G、A等位基因频率分别为74.6%(373/500)、22.4%(112/500)、3.0%(15/500), 85.8%(858/1 000)、14.20%(142/1 000)，健康对照组分别为79.2%(396/500)、19.0%(95/500)、1.80%(9/500), 88.70%(887/1 000)、11.30%(113/1 000)，两组间差异无统计学意义(χ² 值分别为3.584和1.713，P均>0.05)；胃癌组TNF-α、PGI、PGII和PGI/PGII比值分别为(1.03±0.31) μg/L、(84.24±24.81) μg/L、(23.04±4.95) μg/L和3.85±1.49，健康对照组分别为(0.53±0.21) μg/L、(130.27±25.58) μg/L、(20.83±5.83) μg/L和6.45±1.09，两组间差异均有统计学意义(Z=23.614，t值分别为28.882，8.240，22.363，P均<0.01)；TNF-α、PGI及PGI/PGII比值在胃癌组不同基因型(F值分别为180.511、72.840、36.110) 及其不同临床分期(F值分别为34.378、30.981、26.084)患者中的差异均有统计学意义(P均<0.01)，而与PGII水平差异无统计学意义(P均>0.05)；TNF-α与PGI及PGI/PGII比值呈明显负相关(r分别为-0.748、-0.704，均P< 0.01)。

TNF-α-308基因多态性可能不是胃癌的易感性因素，其通过调节TNF-α水平参与胃癌发生发展。TNF-α水平变化影响血清PG表达，胃癌组患者不同基因型及临床分期的PGI和PGI/PGII比值明显不同，用血清PG筛查和诊断胃癌时，应注意PG受TNF-α调控影响。

To investigate association between tumor necrosis factor-alpha-308 polymorphism(TNF-α-308) and serum level of pepsinogen (PG) in patients with gastric cancer.

Human DNA samples were obtained from patients with gastric cancer (n=500) and people who have conducted health examination (n=500). All subjects were genotyped by polymerase chain reaction-restriction fragement length polymorphism analysis. Frequencies of genotypes and alleles were analyzed. TNF-α-308 in relation with the serum level of PG.

Frequency of genotype and allele were 74.60%(373/500), 22.40%(112/500), 3.00%(15/500), 85.80% (858/1 000) and 14.20%(142/1 000) in patients with gastric cancer respectively, and 79.20%(396/500), 19.00%(95/500), 1.80%(9/500), 88.70%(887/1 000) and 11.30%(113/1 000) in health group respectively. There was no significant difference between the two groups (χ²=3.584, 1.713; P>0.05). Compared with health group TNF-α, PGI, PGII and PGI/PGII in patients were (1.03±0.31) μg/L, (84.24±24.81) μg/L, (23.04±4.95) μg/L and 3.85±1.49, which demonstrated a significant difference between the two groups (Z=23.614, t=28.882, 8.240, 22.363; P<0.01). TNF-α, PGI and PGI/PGII ratios in patients of different genotypes(F=180.511, 72.840, 36.110 ) and clinical stages of different genotypes in gastric cancer (F=34.378, 30.981, 26.084) were significantly different (P<0.01), but no significant difference was noticed in the level of PGII (P>0.05). Pearson analysis showed that the level of TNF-α had negative correlation with PGI and PGI/PGII respectively (r=-0.748, -0.704; P<0.01).

TNF-α-308 polymorphism is unlikely to directly cause gastric cancer, whereas it may be involved in the occurrence and development of gastric cancer. The change of TNF-α level which affect the serum level of pepsinogen in patients with gastric cancer through TNF-α level, so that the PGI and PGI/PGII ratios of different genotypes and clinical stages of different genotypes in gastric cancer patients are significantly different, Therefore, when PG is applied in screening and diagnosis of gastric cancer, considerations should be given to the effects of TNF-α on PG regulation.