福建省安溪县食管癌高发影响因素的研究
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摘要
目的：
初步探讨福建省安溪县食管癌高发的影响因素，为食管癌高发区制定综合防制措施提供理论的依据。
方法：
采用1:1配对病例对照研究方法，对237例食管癌患者及与之在年龄、性别和居住地相匹配的对照分别使用食管癌影响因素调查表和家系健康状况调查表进行问卷调查，分析安溪县食管癌高发的影响因素。同时采用免疫组化S-P法对部分调查对象的食管组织标本中的三种细胞周期G_1期调节因子p53、p16及CyclinD1进行检测。采用多元统计方法综合评价环境、遗传、基因这三个因素在食管癌发生过程中的作用大小及作用特点。
结果：
(1)1:1配对病例-对照研究的结果表明：多因素条件Logistic回归分析结果显示：食盐量、性格内向、吸烟量、一级亲属食管癌家族史、病前10～20年常食用油炸食品、红薯、腌菜是食管癌发生的危险因素，而饮茶、饮用清洁水、常吃豆制品、水果是保护因素。
(2)遗传流行病学研究的结果表明：安溪县食管癌具有家族聚集现象，根据Falconer多基因易患性阈值模型计算，安溪县食管癌一级亲属的遗传度为46.5±6.7％。同胞中食管癌的分离分析及根据Penrose法对遗传模式估计的结果均显示食管癌属于多基因疾病。
功戈礴罗
(3)细胞周期G1期相关调节因子检测的结果表明:病例中p53、Cycl inDI、p16三种
蛋白的异常表达率均明显高于正常对照，差别有统计学意义。
(4)遗传、基因与环境因素综合分析的结果表明:在控制基因蛋白表达的影响后，对食
管癌发病有影响的因素为常吃红薯、吸烟、食管癌家族史、饮茶、常吃豆制品等，其
中常吃红薯、吸烟、食管癌家族史为食管癌发生的危险因素，而饮茶、常吃豆制品为
保护因素:当控制环境因素和家族史的影响后，对食管癌发病有影响的基因为p53高
表达及pl6表达缺失，且二者均为危险因素，而CyclinDI对食管癌的作用不明显。
(5)影响因素之间的交互作用分析的结果表明:多个危险因素同时存在，不但可以提
高患食管癌的危险，而且能拮抗饮茶的保护作用。进一步对影响因素之间的交互作用
效应的分析结果表明:环境危险因素(如吸烟、常吃红薯)、食管癌家族史与易感型
基因蛋白(如p53蛋白高表达、P16蛋白表达缺失)以及环境危险因素与食管癌家族
史之间均存在明显的协同作用，而饮茶与p53蛋白高表达、食管癌家族史之间具有拮
抗作用;没发现饮茶与P16蛋白表达缺失之间有交互作用。
结论:
环境、遗传、基因三个因素在食管癌高发区安溪县起着重要的作用，多个危险因素同
时存在以及基因一环境、基因一遗传、环境一遗传之间的交互作用在食管癌肿瘤的发生过程中
尤为重要，因此，在制定食管癌防治措施时，应根据上述三个因素的作用特点，采取综合
性的防制措施:(1)改变不良的行为习惯，调整膳食结构，平衡营养。(2)以年龄大于45
岁，并有以下特征之一者(有食管癌家族史，暴露于多个危险因素，或携带危险基因型)
作为高危人群，利用己知的保护因素(如饮茶、常吃豆制品、蔬菜水果、饮用清洁水等)
加以干预，达到降低食管癌发病的目的。(3)应用简便可靠的筛检方法和诊断方法，在高
危人群中开展预防性普查，做到早发现、早诊断、早治疗，从而提高食管癌患者的生存率
和生活质量。
Objective
To explore the risk factors of esophageal cancer in Anxi of Fujian Province, a high-accident area for esophageal cancer in China, so as to provide evidences for making the integrated preventive measures for esophageal cancer in the high accident place.
Methods
Using case-control study, we investigated 237 pairs about their environmental exposures and disease history of the family, and analyzed the risk factors of esophageal cancer. Meanwhile, I immunohistochemically examined p53, p!6 and CyclinDl protein expressions in 47 patients and 50 controls to analyze the association between those protein expressions and esophageal cancer. The multivariate analysis methods were used to assess the roles of environmental factors, inheritance and genes expression in the progress of esophageal cancer.
Results
(1) By fitting condition logistic regression model, it has showed that the risk factors of esohphageal cancer included over consumption of salt,
introversion, smoking, family history of esophageal cancer and often intaking fried food, potato and pickled vegetables in the last 20 years prior to the diagnosis of esophageal cancer, and the protective factors of esophageal cancer were tea drinking, pure water, fruit and bean products.
(2) Genetic epidemiology study showed that esophageal cancer possessed the character of familial aggregation in Anxi. According to Falconer' s threshold model of polygene liability, the heritability of patients' first grade blood was 46.5±6.7%. Both of the results of Segregation analysis and Penrose' method analysis showed that the mode of inheritance of esophageal cancer in a moderately high-incidence area of Fujian province coincided with a mode of polygenetic inheritance.
(3) The result of immunohistochemistry showed that the alteration rates of the p53 protein, p16 protein and CyclinDl protein were significantly higher in squamous-cell carcinoma of the oesophagus than in normal esophagus.
(4) Gene, environmental exposure and inheritance comprehensive analysis showed that the risk factors of esohphageal cancer were often intaking potato, smoking, family history of esophageal cancer, overexpression of p53 protein and absent expression of p16 protein, and the protective factors of esohphageal cancer were tea drinking and bean products.
(5)The analysis of gene-environment interactions showed that exposure more than one risk factors can not only increase the risk of esophageal cancer, but also decrease the protective effect of tea drinking. The further analysis of the interaction model between gene and environmental exposures, gene and inherence, environmental exposures and inherence showed that the interactions between over expression of p53 and smoking, often intaking potato, or family history of esophageal cancer presented synergism, so did the association between absent expression of p16 protein and smoking, often intaking potato, or family history of esophageal cancer, in contrast, tea drinking can
antagonize the effects of over expression of p53 and family history of esophageal cancer, there was no relation between tea drinking and absent expression of p16 protein.
Conclusion
Environmental factors, inheritance and genes play important roles in the progress of esophageal cancer in the high accident area of Fujian province, and their interactions do especially. The high risk population should be of having the characteristics of risk genetype, exposure to more than one risk factors or have genetic background. To prevent esophageal cancer effectively, we should do follows: First, advising the population living in high accident area to change their behavior habits and adjust meal construction. Second, preventing the high risk population from exposing to environmental risk factors, or using environmental protective factors to intervene. Such studies are expected to shed light on the etiology and prevention of esophageal cancers in the high accident area, and more researches are needed to understand the relationship among environmental exposures, inheritanc
初步探讨福建省安溪县食管癌高发的影响因素，为食管癌高发区制定综合防制措施提供理论的依据。
方法：
采用1:1配对病例对照研究方法，对237例食管癌患者及与之在年龄、性别和居住地相匹配的对照分别使用食管癌影响因素调查表和家系健康状况调查表进行问卷调查，分析安溪县食管癌高发的影响因素。同时采用免疫组化S-P法对部分调查对象的食管组织标本中的三种细胞周期G_1期调节因子p53、p16及CyclinD1进行检测。采用多元统计方法综合评价环境、遗传、基因这三个因素在食管癌发生过程中的作用大小及作用特点。
结果：
(1)1:1配对病例-对照研究的结果表明：多因素条件Logistic回归分析结果显示：食盐量、性格内向、吸烟量、一级亲属食管癌家族史、病前10～20年常食用油炸食品、红薯、腌菜是食管癌发生的危险因素，而饮茶、饮用清洁水、常吃豆制品、水果是保护因素。
(2)遗传流行病学研究的结果表明：安溪县食管癌具有家族聚集现象，根据Falconer多基因易患性阈值模型计算，安溪县食管癌一级亲属的遗传度为46.5±6.7％。同胞中食管癌的分离分析及根据Penrose法对遗传模式估计的结果均显示食管癌属于多基因疾病。
功戈礴罗
(3)细胞周期G1期相关调节因子检测的结果表明:病例中p53、Cycl inDI、p16三种
蛋白的异常表达率均明显高于正常对照，差别有统计学意义。
(4)遗传、基因与环境因素综合分析的结果表明:在控制基因蛋白表达的影响后，对食
管癌发病有影响的因素为常吃红薯、吸烟、食管癌家族史、饮茶、常吃豆制品等，其
中常吃红薯、吸烟、食管癌家族史为食管癌发生的危险因素，而饮茶、常吃豆制品为
保护因素:当控制环境因素和家族史的影响后，对食管癌发病有影响的基因为p53高
表达及pl6表达缺失，且二者均为危险因素，而CyclinDI对食管癌的作用不明显。
(5)影响因素之间的交互作用分析的结果表明:多个危险因素同时存在，不但可以提
高患食管癌的危险，而且能拮抗饮茶的保护作用。进一步对影响因素之间的交互作用
效应的分析结果表明:环境危险因素(如吸烟、常吃红薯)、食管癌家族史与易感型
基因蛋白(如p53蛋白高表达、P16蛋白表达缺失)以及环境危险因素与食管癌家族
史之间均存在明显的协同作用，而饮茶与p53蛋白高表达、食管癌家族史之间具有拮
抗作用;没发现饮茶与P16蛋白表达缺失之间有交互作用。
结论:
环境、遗传、基因三个因素在食管癌高发区安溪县起着重要的作用，多个危险因素同
时存在以及基因一环境、基因一遗传、环境一遗传之间的交互作用在食管癌肿瘤的发生过程中
尤为重要，因此，在制定食管癌防治措施时，应根据上述三个因素的作用特点，采取综合
性的防制措施:(1)改变不良的行为习惯，调整膳食结构，平衡营养。(2)以年龄大于45
岁，并有以下特征之一者(有食管癌家族史，暴露于多个危险因素，或携带危险基因型)
作为高危人群，利用己知的保护因素(如饮茶、常吃豆制品、蔬菜水果、饮用清洁水等)
加以干预，达到降低食管癌发病的目的。(3)应用简便可靠的筛检方法和诊断方法，在高
危人群中开展预防性普查，做到早发现、早诊断、早治疗，从而提高食管癌患者的生存率
和生活质量。
Objective
To explore the risk factors of esophageal cancer in Anxi of Fujian Province, a high-accident area for esophageal cancer in China, so as to provide evidences for making the integrated preventive measures for esophageal cancer in the high accident place.
Methods
Using case-control study, we investigated 237 pairs about their environmental exposures and disease history of the family, and analyzed the risk factors of esophageal cancer. Meanwhile, I immunohistochemically examined p53, p!6 and CyclinDl protein expressions in 47 patients and 50 controls to analyze the association between those protein expressions and esophageal cancer. The multivariate analysis methods were used to assess the roles of environmental factors, inheritance and genes expression in the progress of esophageal cancer.
Results
(1) By fitting condition logistic regression model, it has showed that the risk factors of esohphageal cancer included over consumption of salt,
introversion, smoking, family history of esophageal cancer and often intaking fried food, potato and pickled vegetables in the last 20 years prior to the diagnosis of esophageal cancer, and the protective factors of esophageal cancer were tea drinking, pure water, fruit and bean products.
(2) Genetic epidemiology study showed that esophageal cancer possessed the character of familial aggregation in Anxi. According to Falconer' s threshold model of polygene liability, the heritability of patients' first grade blood was 46.5±6.7%. Both of the results of Segregation analysis and Penrose' method analysis showed that the mode of inheritance of esophageal cancer in a moderately high-incidence area of Fujian province coincided with a mode of polygenetic inheritance.
(3) The result of immunohistochemistry showed that the alteration rates of the p53 protein, p16 protein and CyclinDl protein were significantly higher in squamous-cell carcinoma of the oesophagus than in normal esophagus.
(4) Gene, environmental exposure and inheritance comprehensive analysis showed that the risk factors of esohphageal cancer were often intaking potato, smoking, family history of esophageal cancer, overexpression of p53 protein and absent expression of p16 protein, and the protective factors of esohphageal cancer were tea drinking and bean products.
(5)The analysis of gene-environment interactions showed that exposure more than one risk factors can not only increase the risk of esophageal cancer, but also decrease the protective effect of tea drinking. The further analysis of the interaction model between gene and environmental exposures, gene and inherence, environmental exposures and inherence showed that the interactions between over expression of p53 and smoking, often intaking potato, or family history of esophageal cancer presented synergism, so did the association between absent expression of p16 protein and smoking, often intaking potato, or family history of esophageal cancer, in contrast, tea drinking can
antagonize the effects of over expression of p53 and family history of esophageal cancer, there was no relation between tea drinking and absent expression of p16 protein.
Conclusion
Environmental factors, inheritance and genes play important roles in the progress of esophageal cancer in the high accident area of Fujian province, and their interactions do especially. The high risk population should be of having the characteristics of risk genetype, exposure to more than one risk factors or have genetic background. To prevent esophageal cancer effectively, we should do follows: First, advising the population living in high accident area to change their behavior habits and adjust meal construction. Second, preventing the high risk population from exposing to environmental risk factors, or using environmental protective factors to intervene. Such studies are expected to shed light on the etiology and prevention of esophageal cancers in the high accident area, and more researches are needed to understand the relationship among environmental exposures, inheritanc
引文
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