胃癌易感基因筛选及多基因危险度分析

李鹏飞; 冯靖宇; 严滢滢; 符刚; 沈孝兵

胃癌易感基因筛选及多基因危险度分析

Screening of Susceptibility Genes and Multi-gene Risk Analysis in Gastric Cancer

摘要

摘要:
目的探讨我国汉族人群胃癌患者遗传易感基因,并进行多基因危险度分析。

方法采用1:1配对病例对照研究方法,收集南京市汉族人群原发性胃癌患者585例和相应非肿瘤及非消化道疾病患者为研究对象,应用限制性片段长度多态性聚合酶链反应(PCR-RFLP)和基因特异性聚合酶链反应(AS-PCR)技术分析CYP2E1、GSTM1、GSTT1、NAT2、ALDH2、MTHFR、XRCCl、IL-1β、VDR、TNF等基因型别;以条件logistic回归模型对基因及基因间的交互作用进行分析,选出易感基因,多基因联合作用危险度分析统计模型对选出的危险因素进行多基因危险度评价。

结果原发性胃癌遗传易感因素有8项,分别是CYP2E1(c1/c1)、NAT2表型(慢乙酰化型)、MTHFRA1298C(A/C)、IL-1β(C/T)、NAT2M2(A/A)、XRCC1194(T/T)、NAT2M1(T/T)、VDR TaqI(T/T)。利用多基因联合作用危险度分析模型对多基因危险度评价分析,可以更直观地发现多基因组合的OR值与其基因频率存在高度相关性,即随易感基因的增加,易感基因组合危险度分布曲线会向更加危险的方向移动。并呈现一定的量化关系。

结论通过对筛选出的易感基因进行多基因危险度分析,可更有效地推进对汉族人群中胃癌的高危人群识别及对其采取预防和干预措施。

Abstract:
Objective To explore the relations between genetic polymorphism and susceptibility to gastric cancer in Chinese population,and to study the action of genetic factors in development of gastric carcinoma.

Methods A case-control study was performed in 585 controls without tumor matched to 585 original gastric cancer patients in Nanjing city.The genotypes of CYP2E1,GSTM1,GSTT1,NAT2,ALDH2,MTHFR,XRCCl,IL-1β,VDR and TNF were detected by molecular biological techniques (PCR-RFLP and AS-PCR).Sole gene and gene-gene interactions were analyzed by Logistic regression model,and the multi-gene risk of susceptibility genes were analyzed by a multi-gene risk analysis statistic model proposed by Demchuk E.

Results The genetic risk factors associated with primary gastric cancer susceptibility were CYP2E1(c1/c1),NAT2 phenotype (slow acetylator),MTHFRA1298C (A/C),IL-1β(C/T),NAT2M2(A/A),XRCC1194(T/T),NAT2M1(T/T),VDR TaqI (T/T).The multigene risk analysis showed there was close relation between the OR of polygene combination and the genotype frequency.The OR increased along with the susceptibility gene.

Conclusion This new analyze model is helpful to screen and protect the high-risk group of gastric cancer.

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