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细胞色素P4501A1基因多态性在胃癌发生中的交互作用
Research on the interaction models of cytochrome P450 1A1 polymorphism (s) in the agents of stomach cancer
【摘要】 目的 探讨CYP1A1突变基因型与吸烟、饮酒因素对胃癌发生的交互作用及作用方式。方法 以社区为基础的病例对照研究 ,病例为胃镜及病理确诊的肠型胃癌 ,共 112例 ,以同期上消化道肿瘤病例的“健康”同胞、配偶和配偶的同胞为对照组 ,共 6 76例 ,用多聚酶链反应和限制性片段长度多态性法检测其基因型 ,多因素logistic回归模型分析与胃癌的相关性。结果 在调整混杂因素的影响后 ,未见CYP1A1突变基因型与胃癌危险性之间有统计学关联 ;但CYP1A1基因型与吸烟对胃癌发生有明显交互作用 ,显著增加胃癌的危险性 ,交互作用系数γ为 2 82 ,OReg值为 5 0 0 ,为 2型交互作用中的超相乘模型。进一步分析剂量反应关系显示 :突变基因型与吸烟量、开始吸烟年龄均呈“低暴露 基因效应”方式 ,即随着暴露剂量的增加 ,交互作用的强度逐渐降低。CYP1A1突变基因型与饮酒史的交互作用有减弱效应 ,OReg值为 2 2 2 ,γ为 0 46 ,但呈“高暴露 基因效应”。结论 CYP1A1突变基因型与吸烟、饮酒对胃癌均有交互作用 ,但交互作用的方式不同。这些结果提示CYP1A1突变基因型的个体应完全戒烟、限制大量饮酒 ,以预防胃癌的发生。
【Abstract】 Objective To explore the interaction models between CYP1A1 mutation polymorphism(s) and ever tobacco smoking, ever alcohol drinking in the occurrence of intestinal stomach cancer. Methods Using community based case control design, we have identified 112 intestinal types of stomach cancer patients with endoscopy and pathology diagnosis during Jan 1997 and Dec 1998 A total of 676 controls were selected from the spouse and siblings of cases or the siblings in law, who have no history of digestive system cancers PCR RFLP technique was used to detect genotyping of the samples and multiple logistic regression analysis was performed to adjust for important confounding factors. Results Mono variable analysis shows that frequency of CYP1A1 mutation genotype has no significant difference in cases and controls Both CYP1A1 mutation and ever tobacco smoking shows a significant gene environment interaction Interaction index (γ) values was 2 82, OR eg values was 5 00 It means that a super multiplicative type 2 interaction occurs Furthermore, the results also showed that CYP1A1 mutation genotype had a low exposure gene effect interaction with both tobacco smoking (pack year) and beginning age of smoking A decreasing interaction was found between CYP1A1 genotype and ever alcohol drinking, γ was 0 46, OR eg values was 2 22 Furthermore, a high exposure gene effect interaction was found in CYP1A1 mutation with alcohol drinking amount (kg year). Conclusions CYP1A1 polymorphism(s) had shown significant gene environment interaction with both tobacco smoking and alcohol drinking in the occurrence of stomach cancer It suggests that person carrying mutation genotype must cease tobacco smoking completely and diminish amount of drinking alcohol in order to prevent stomach cancer
【Key words】 Cytochrome P 450 CYP1A1; Polymorphism (genetics); Stomach neoplasms;
- 【文献出处】 中华预防医学杂志 ,Chinese Journal of Preventive Medicine , 编辑部邮箱 ,2001年03期
- 【分类号】R735.2
- 【被引频次】21
- 【下载频次】319