中国北方人群谷胱甘肽转硫酶P1基因多态性及其与胃癌遗传易感性的关系

为了分析中国北方人群谷胱甘肽转硫酶P1基因(glutathione-S-transferase P1, GSTP1)多态性分布, 同时探讨GSTP1基因多态性及其与幽门螺杆菌(H. pylori)既往感染联合作用对胃癌发病风险的影响, 采用多聚酶链反应-限制性片段长度多态性(PCR-RFLP)技术检测1,612例外周血DNA GSTP1的多态性; 采用ELISA方法检测血清H. pylori IgG。结果显示, (1) 中国北方人群GSTP1基因Val等位基因分布频率为22%, 胃癌高、低发区GSTP1 Val等位基因分布频率有显著性差异(0.23/0.20); (2) 以Ile/Ile基因型为参照组与其他两种基因型比较进行胃癌的风险分析, 结果显示携带Val/Val基因型的个体患胃癌的危险性最大, 其OR为5.588 (3.256 ~ 9.591); 携带Val等位基因的个体患胃癌危险性是非携带Val等位基因个体的1.587倍; (3) 以H. pylori IgG(-)并携带GSTP1基因纯合野生型(Ile/ Ile)的个体为参照, H. pylori IgG(+)并携带纯合多态基因型(Val/Val)的个体患胃癌的风险最高, OR为17.571(6.207 ~ 49.742)。说明GSTP1 Val等位基因的分布存在人群及地区差异。携带GSTP1 Val等位基因的个体胃癌发病风险增高。GSTP1 Val等位基因纯合型与H. pylori感染对于胃癌的发生具有交互作用。

A molecular epidemiological study on the relationship between the polymorphism of GSTP1 and susceptibility to gastric cancer in northern Chinese

We analyzed the distribution of glutathione-S-transferase P1 gene (GSTP1) polymorphism in a population from northern China and the relationship between the polymorphic BsmAI site in its exon 5 and gastric cancer susceptibility and evaluated the combined effect of GSTP1 polymorphism and H. pylori infection on gastric cancer. Blood samples were taken from 1,612 subjects in areas of high and low incidence of gastric cancer. Polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) were performed to analyze the genotype of a GSTP1 polymorphism in exon 5 (Ile105Val). Serum levels of anti-H. pylori IgG were measured by enzymed-linked immunosorbent assay. We found that the GSTP1 Val variant allele frequency was 22%, which was significantly different from the Western people. There was a significant difference in GSTP1 allele gene distribution between the area of high incidence of gastric cancer(23%) and low incidence(20%). The frequency of GSTP1 Val/Val genotype was statistically higher in the gastric cancer group compared to the non-gastric cancer population. Analysis showed a statistically significant 1.587-fold increase in gastric cancer risk associated with the GSTP1 Val allele. Moreover, there was a statistically significant interaction (odds ratio, 17.571; 95% confidence interval, 6.207 - 49.742) between GSTP1 Val/Val genotype and positive H. pylori IgG status. Our results indicate that the distribution of GSTP1 polymorphism has geographic differences. Individuals with the GSTP1 Val allele gene show an increased risk for gastric cancer. Association of the GSTP1 (Val/Val) genotype with H. pylori IgG positive status could significantly increase gastric cancer risk.