PTPN11第3内含子基因多态性及H.pylori感染与广西柳州地区胃癌易感性研究

PTPN11 Gene Polymorphisms, Helicobacter pylori Infection and Susceptibility to Gastric Cancer in Liuzhou Area of Guangxi Province in China

目的探讨蛋白酪氨酸磷酸酶非受体型11(PTPN11)基因多态性及幽门螺杆菌(H.pylori)感染与广西柳州地区胃癌易感性的相关性。方法通过PCR检测H.pylori的尿素酶B亚单位(UreB)基因和两步法聚合酶链反应(PCR-CTPP)对广西柳州地区238例胃癌患者及112例健康对照者的PTPN11基因第3内含子2460位点进行单链构象多态性分析(SNP)。结果胃癌组和对照组H.pylori(+)者分别为142例(59.7%)和54例(48.2%),H.pylori(-)者分别为96例(40.3%)和58例(51.8%),H.pylori感染率在两组间差异有统计学意义(P<0.05)。胃癌组和对照组PTPN11基因在该位点的基因型频率分布符合遗传平衡状态且差异无统计学意义(P>0.05),但两组间的等位基因分布差异有统计学意义(P<0.05)。与G/G型相比,G/A型和A/A型不能减低胃癌的发病风险(G/A型:OR=0.642,95%CI:0.397～1.039;A/A型:OR=0.399,95%CI:0.097～1.641);但将G/A型和A/A型合并后与G/G型相比,带有A基因的个体患胃癌的风险显著降低(OR=0.620,95%CI:0.388～0.992)。根据发病年龄、性别、吸烟史、饮酒史和H.pylori感染对胃癌的易感性进行的分层分析发现,PTPN11基因该位点SNP与胃癌的年龄、性别、吸烟史以及饮酒史无关,H.pylori阳性的A基因携带者相对于G/G型个体患胃癌的风险减少到0.52倍(OR=0.521,95%CI:0.274～0.990)。结论广西柳州地区PTPN11基因第3内含子2460位点A基因携带者能明显降低胃癌的发病风险,H.pylori感染与该位点G/G基因型之间存在交互作用。

Objective To investigate the association between PTPN11 （protein-tyrosine phosphatase, non-receptor type 11） gene polymorphisms, Helicobacter pylori （H. pylori） infection and susceptibility to gastric cancer in Liuzhou area of Guangxi Province in China. Methods PTPN11 gene polymorphism at position 2460 in intron 3 was genotyped in 236 gastric cancer and 112 age-matched normal controls using the polymerase chain reaction with confronting two-pair primers （PCR-CTPP）. Results The allele and genotype frequency were in HardyWeinberg equilibrium by comparison with that of the corresponding theoretical distribution in gastric patients and controls. There were significant differences in allele frequency at position 2460 in intron 3 of the PTPNll between patients and control group （P〈0.05）, however, there was no difference in the frequency of genotype between the 2 groups （P〉 0.05）. Compared with G/G genotype, A/A and G/A genotype could not reduce the risk of gastric carcinoma （OR= 0.642, 95%CI： 0.397-1.039; 0R=0.399, 95%C1： 0.097-1.64, respectively）. A-allele carriers （G/A or A/A genotypes） were at a lower risk of having gastric carcinoma （0R=0.620, 95%CI： 0.388-0.992） than the patients with GG genotype. When stratified for status, PTPN11 polymorphism was not associated with age, gender, history of smoking and drinking in both cancer patients and healthy controls. However, the A-allele carriers with H. pylori infection were at a lower risk of having gastric cancer （OR =0.521, 95%C1： 0.274-0.990）. Conclusion In Liuzhou area, individuals with PTPNll gene polymorphism at the site of 2460 in intron 3 are at lower risk of having gastric cancer. G/G genotype might contribute to the development of gastric cancer cause by H.pylori infection.