EB病毒、幽门螺杆菌cagA和vacA基因型感染与胃癌的关系研究

Relationship Study of EBV,H· Pylori CagA and H· Pylori VacA Infection with Gastric Cancer

目的探讨EB病毒,H.pylori cagA基因、vacA基因在胃癌发生发展中的作用及三者关系。方法以病理活检确诊的胃癌病人为实验组(46例),癌前病变(包括肠化生、萎缩性胃炎、非典型增生等)病人对照组(43例),胃镜下取胃癌组织,采用PCR体外扩增方法,检测胃癌组织及癌前病变组织中EBV-DNA,用快速尿素酶试验检测HP,阳性病人做PCR体外扩增,并用PCR法进行H.pylori cagA和vacA基因检测,进行基因分型。结果(1)对照组2例,阳性率为4.6%(2/43);实验组10例,阳性率为21.7%(10/46)。实验组与对照组差异有统计学意义(P<0.05)。EBVaGC(EBVassociated gastric carcinoma,EBVaGC)和EBVnGC(EBV negative gastric careinoma,EBVnGC)在年龄、病理类型方面差异无显著性(P>0.05);在性别方面差异有统计学意义,男性EBV阳性率高于女性(P<0.05)。(2)等级统计分析表明,EBV感染与慢性胃炎→萎缩→肠化生→高中低分化胃癌演变过程中呈正相关(r=0.25465,P=0.0160)。(3)实验组H.pylori感染率60.9%(28/46),对照组H.pylori感染率37.2%(16/43),实验组与对照组差异有统计学意义(P<0.05)。(4)慢性浅表性胃炎、萎缩、肠化生、胃癌各组织中H.pylori与cagA和vacA表达均呈正相关(P<0.01)。(5)H.pylori、H.pylori cagA、vacA阳性和阴性在性别、年龄差异无显著性(P>0.05),但在病理类型方面H.pylori、cagA、vacA阳性和阴性有统计学差异(P<0.01.)。(6)相关性分析表明EBV感染与H.pylori cagA呈正相关(P=0.0287,r=0.23199),与H.pylori vacA无相关性(P=0.8094,r=0.02595)。结论(1)EBV感染与胃癌的发生发展有一定相关性,EBVaGC好发于男性,EBV感染与慢性胃炎→萎缩→肠化生→胃癌演变过程中呈正相关。但EBV感染与胃癌病人年龄、病理类型、无明显相关性。(2)H.pylori感染与胃癌的发生密切相关,H.pylori感染与胃癌的临床病理类型相关,但H.pylori感染与胃癌病人性别、年龄无明显相关性。(3)胃癌发生中EBV感染和cagA的表达呈正相关,与vacA无明显相关性。

Abstract Objective To study the role of Epstein - Barr virus （EBV） , Helicobacter pylofi cagA （ H · pylori cagA ） and vacA genes （ H· pylori vacA） infection in the occurrence and development of gastric cancer and their relationship. Abstract Objective Experiment group （ n = 46 ） was formed by patients with gastric cancer confirmed by pathological biopsy while control group （ n = 43 ） Was fromed by patients with precancerous lesion （ including intestinal metaplasia, atrophic gastritis, atypical hyperplasia and so on） ; gastric cancer tissue was collected under gastroscope and PCR Vitro Amplification was applied in detecting EBV - DNA in gastric cancer tissue and precancerous lesion tissue and Fast Urease Test in detecting HP, the positive patients, after PCR Vitro Amplification, received detection of H pylori cagA and vacA by PCR, and genotyping was made then. Results （ 1 ） The positive rate of control group was 4.6% （2/43） and that of experiment group was 21.7% （ 10/46 ）, the difference between the 2 groups was of statistical significance （ P 〈 0. 05 ） ; BEVaGC （ BEV associated with gastric cancer） showed no obvious difference from BEVnGC （ BEV negative in gastric cancer） in age and pathological typing （ P 〉 0. 05 ） ; there existed a statistical difference in sex , the positive rate of EBV in males was higher than that in females （ P 〈 0. 05 ） ; （ 2 ） Statistical analysis of grading showed BEV infection played a positive correlation in the development of gastric cancer （ from chronic gastritis to atrophic gastritis, to intestinal metaplasia, to well, moderately and poorly differentiation ） （ r = 0. 25465, P = 0. 0160 }. （ 3 ） The infective rate of H · pyloft in experiment group was 60.9% （28/46） while that in control group was 37.2% （ 16/43 ）, the difference between the 2 groups was of statistical significance （ P 〈 0. 05 ）. （ 4 ） H · pylori were positively correlated with eagA and vacA in the tissues of chronic superficial gastritis （r=0.52, r= 0.59, P〈0.01）, atrophy （r=0.71, r=0. 89, P〈0.01）, intestinal metaplasia [r =0.90, r=0.87, P〈0.01） and gastric cancer （r=0.91, r=0.96, P〈0.01）. （5） There existed no obvious difference between the positive and negative H · pylori, H . pylori cagA and vaeA in sex and age （ P 〉 0. 05 ） but a statistical difference in pathological typing （ P 〈 0. 01 ）. （ 6 ） Correlative analysis showed EBV infection was positively correlated with H · pylofi cagA （ P =0.0287, r =0.23199） but had no correlation with H · pylori vacA {P=0.8094, r=0.02595）. Conclusions （1） EBV infection has certain correlation with the occurrence and development of gastric cancer and EBVaGC was more often found in males ; EBV infection is positively correlated with development of gastric cancer （ from chronic gastritis to atrophic gastritis, to intestinal metaplasia, to gastric cancer） but is not obviously correlated with the age and pathological typing of the patients with gastric cancer. （2 ） H · pylori infection is closely correlated with the occurrence of gastric cancer, it is correlated with clinic pathological typing of gastric cancer but not correlated with the sex and age of the patients with gastric cancer. （ 3 ） EBV infection of gastric cancer is positively con-dated with cagA and not with vaeA.