错配修复基因hMSH2多态性IVS+9C→G与胃癌发病关系的研究

Etiological role of polymorphism IVS+9C→G in hMSH2 gene in gastric cancers

目的:探讨错配修复基因hMSH2多态位点IVS1+9C→G在胃癌发病中的作用。方法:应用PCRDHPLC和DNA序列分析技术检测126例健康人、72例散发性胃癌患者和71例有家族史胃癌患者的外周血DNA,采用病例对照研究方法分析hMSH2基因IVS1+9C→G多态性与胃癌发病的关系。结果:42例(33.3%)健康人、29例(40.3%)散发性胃癌患者和31例(43.7%)有家族史的胃癌患者检出hMSH2基因IVS1+9C→G。低龄(<50岁)胃癌患者中hMSH2基因IVS1+9C→G检出率(60%)高于正常人群(33.3%),P<0.05;在散发性胃癌患者中,病理分化程度低者其检出率(66.7%)高于分化程度较高者(19.2%),P<0.01;有家族史胃癌患者的检出率(43.7%)虽高于健康人(33.3%),但无显著性差异(P>0.05)。结论:hMSH2基因多态位点IVS1+9C→G可能影响部分胃癌的发病年龄,并对胃癌的分化程度起一定作用。提示hMSH2基因IVS1+9C→G的筛查可能成为胃癌风险评估的指标。

Objective: To investigate the etiological role of polymorphism IVS1+9C→G in hMSH2 gene in gastric cancers. Methods: A case-control study has been taken on subjects included 72 sporadic gastric, 71 familial gastric cancers and 126 healthy individual controls. Genomic DNA was extracted from peripheral white cell of all subjects. The polymorphism was detected by a PCR-based DHPLC analysis and verified by DNA sequencing. Results: The polymorphism IVS1+9C→G in hMSH2 gene was detected in 33.3%(42/126) Healthy individuals, 40.3%((29/72 ))sporadic gastric and 43.7%(31/71 )familial gastric cancers. Significant difference existed between cancers at young age (<50 years) (60%)and the controls(33.3%)(OR=3.00, 95%CI: 1.04～8.80). Furthering statistics based on histological type revealed that the frequency of this polymorphism was higher in poorly differentiated-type cancers (66.7%)than in differentiated cancers(19.2%),P<0.01. No significant difference was found between familial gastric cancers(43.7%) and controls(33.3%). Conclusion:The genetic polymorphism IVS1+9C→G in hMSH2 gene may play a role in the onset and the differentiation in sporadic gastric cancers, especially in cancers at lower age. Determination of this polymorphism may be suitable to identify individuals with increased risk of gastric cancer.