基因多态性及常见危险因素与胃癌易患性的研究

目的探讨中国汉族人群细胞色素P450(CYP)1A1基因型、谷胱甘肽巯基转移酶(GST) M1基因型及常见危险因素与胃癌易患性的关系,为胃癌高危人群的确定和胃癌的一级预防提供分子生物学手段。方法所有研究对象经胃镜和病理检查分为胃癌(GC,仅包括胃腺癌)组102例、慢性萎缩性胃炎(CAG)组110例、慢性浅表性胃炎(CSG)组110例、胃溃疡(GU)组62例、十二指肠溃疡(DU)组62例及正常对照组62例。采用统一的调查表对每个研究对象进行调查,调查项目包括年龄、性别、学历、职业、吸炯史、饮酒史、饮食习惯、肿瘤家族史等。采用序列特异性引物的聚合酶链反应(PCR-SSP)方法检测CYP1A1基因型及GSTM1基因型测定组的基因型频率,ELISA法测定幽门螺杆菌(Hp)感染,病例对照研究方法进行流行病学分析。结果单因素分析显示与胃癌有关联的危险因素为年龄、性别、文化程度、职业、Hp感染、吸烟、CYP1A1 G/G基因型、GSTM1空白基因型,其中大蒜为保护性因素;多因素分析显示与胃癌有关联的危险因素分别为Hp感染、CYP1A1 G/G基因型、GSTM1空白基因型,大蒜仍为保护性因素。CYP1A1 G／G基因型及GSTM1空白基因型对胃癌的发生具有协同作用。Hp感染与CYP1A1 G／G基因型、GSTM1空白基因型对胃癌的发生存在协同作用;吸烟与CYP1A1 G/G基因型、GSTM1空白基因型存在协同作用。结论具有CYP1A1 G/G或GSTM1基因型的个体发生胃癌的危险性增加,而同时有两种基因型的个体发生胃癌的危险性更高,这两种基因型可以认为是胃癌易患性的标志。

The genetic polymorphism and risk factors that associated with the susceptibility of gastric cancer

Objective To explore the association of cytochrome P450(CYP)1A1 and glutathione S-transferase(GST) M1 gene polymorphism and frequent risk factors to the susceptibility of gastric cancer in Chinese Han ethnic group, and to provide molecular methods to define the high risk population of gastric cancer for primary prevention. Methods All subjects were divided into gastric cancer(GC, only include adenocarcinoma) , chronic atrophic gastritis(CAG) , chronic superficial gastritis(CSG), gastric ulcer, dudenal ulcer and normal health control groups determined by endoscopical and histopathological examinations. Life-style data was collected by the questionnaires, including age, sex, education, occupation, smoking and drinking history, dietary habits and family history of cancer etc. CYP1A1 and GSTM1 genotypes were determined by polymerase chain reaction of sequence-specific primers(PCR-SSP). H.pylori infection was detected by enzyme-linked immunosorbent assay. The risk factors were determined by the case control study. Results The risk factors associated with the development of gastric cancer were age, sex, education, occupation, H. pylori infection, tobacco smoke, CYP1A1 G/G genotype and GSTM1 null genotype. Garlic was a protective factor. Multivariate analysis showed that the risk factors were H. pylori infection, CYP1A1 G/G genotype and GSTM1 null genotype with garlic as a protective factor. There were synergistic effects between CYP1A1 G/G and GSTM1 null genotype, H. pylori infection and CYP1A1 G/G genotype, H. pylori infection and GSTM1 genotype, tobacco smoke and CYP1A1 G/G genotype, tobacco smoke and GSTM1 genotype in the development of gastric cancer. Conclusions The CYP1A1 G/G genotype and GSTM1 null genotype are associated with gastric cancer. Individuals with both two genotypes have higher risk of gastric cancer. These two genotypes may be considered as markers associated with increased susceptibility of gastric cancer.