【作者】 张军；

【导师】 杨功焕；

【作者基本信息】 中国疾病预防控制中心 ， 流行病与卫生统计学， 2010， 博士

【摘要】 目的：针对淮河流域癌症高发现象,选取河南省沈丘县作为研究区,综合运用空间流行病学、生态流行病学、环境流行病学、分析流行病学(病例对照研究)方法,对该地区历史和目前工业污染、农业污染、生活污染状况进行综合分析,寻找造成水体污染和三种消化道癌症(食管癌、胃癌、肝癌)高发的污染物及其来源,分析环境污染因素、行为生活方式等因素与三种癌症发生的关系,探索当地可能的致癌因素、促癌因素及保护因素,试图构建和论证从污染到疾病发生的病因链条。方法与结果：1.沈丘县农业污染状况调查收集沈丘县1984-2005年20年间农药化肥使用情况,对资料进行描述性分析。结果显示沈丘县农田中氮素盈余水平从1984年至2005年整体上处于上升态势,2000年以后该地区氮素盈余量处在一个较高的水平之上,并且相当程度上已经达到了危险水平。农药施用量一直处在较高水平,可能造成的污染也处于较高水平。2.沈丘县工业污染状况调查调查沈丘县域内及沙颖河上游1985年以来污染企业的种类、规模、数量及地理分布(包括1985年及以后的现有企业和停产企业),了解污染企业的生产工艺及三废排放概况,分析可能存在的有害物质种类。结果显示沈丘县当前和历史主要污染行业为皮革、造纸、化工、印染和塑料,这些污染企业排放的废水、废渣中含有各种有机污染物、重金属和无机物,有许多物质如氯乙烯、邻苯二甲酸酯、砷等是国际癌症研究中心(IARC)确定的1类或2类致癌物。3.沈丘县消化道癌聚集区环境卫生和环境污染状况调查利用空间热点探测技术,确定沈丘县消化道癌死亡高聚集区和低聚集区,对高低聚集区环境卫生状况、环境污染状况进行调查,分析环境污染与消化道癌聚集性的关系。调查结果显示聚集区基本没有垃圾、污水处理设施,环境卫生状况比较差。聚集区内河流、沟渠、坑塘受污染比例高。10年前、20年前工业污染企业数量与消化道癌聚集性显著相关,OR值分别为5.932(1.411-24.937)和5.218(1.005-27.086)。4.环境水样检测分析根据沈丘县环境调查情况确定采样点,按照标准规范采集沙颍河河水、池塘水、浅井水和深水井水样,用气相色谱-质谱检测环境水样挥发性和半挥发性有机污染物,固相萃取／气相色谱-质谱法测定饮用水中半挥发性有机化合物,高效液相色谱检测环境水样藻毒素。对刘集水样有机污染物全谱分析共检测出390种有机物,其中地表水中228种,井水中232种,且刘集地表水与井水中邻苯二甲酸二丁酯、γ-谷甾醇、岩藻甾醇等成分的峰均显著高于其它成分,提示这些污染物可能成为该地区地表水与井水中所需要优先控制的污染物。环境水样中检测出邻苯二甲酸酯、壬基酚、双酚A等环境内分泌干扰物。藻毒素检测结果发现浓度范围在0-2.298μg/L之间,四种水体年平均藻毒素浓度其大小顺位为河水>池塘水>浅井水>深井水。5.环境水样致癌活性分析采用经优化的Balb／c3T3细胞转化方法,对沈丘县河水及居民饮用水水样进行了细胞毒性和致癌活性检测,发现沈丘县癌症高发地区污染的地面水具有很强的细胞毒性和致癌活性,其在原水浓度下就已具有促进细胞恶性转化的能力。井水的致癌性有随井深的增加而降低的趋势。小于10米的浅井水在高浓缩度下能表现出致癌性,40米深的井水则不具有促细胞转化的能力。6.病例对照研究采取以人群为基础的病例对照研究方法,选取当地30-70岁年龄段的病例和对照,分析沈丘县水源因素、环境因素、行为生活方式等因素与食管癌、胃癌、肝癌发生的关系。食管癌病例对照研究结果显示：食管癌患者周边有污染源水源使用时间、分散式供水时间均高于对照组,使食管癌发生的危险性升高,而对照组周边无污染源水源使用时间显著长于食管癌患者,表现出保护作用；食管癌发生表现出家族聚集性,食管癌患者一级、二级亲属中食管癌发生比例越高,发生食管癌的危险性增加；经常生气、睡眠状况不好、经历负性重大事件等社会精神因素与食管癌的关联具有统计学意义；饮食口味清淡、喜欢吃偏凉食物、较软食物能降低食管癌发生的危险性,饮茶、多摄入薯类、辣椒、大蒜、坚果和水果对食管癌具有保护作用。胃癌病例对照研究结果表明：胃癌病例组周边有污染源水源时间饮用时间、分散式供水时间均高于对照组,显示为危险因素；井周边30米范围内无污染源、饮用深井水则显示出保护作用。胃癌具有家族聚集性,一级亲属胃癌比例高增加胃癌发生的危险性。经常生气、睡眠状况不好使胃癌发生的危险性增加。饮茶、饮食口味清淡、喜欢吃较软食物、多摄入薯类、辣椒、水果对胃癌具有保护作用。肝癌病例对照研究结果发现：肝癌病例组周边有污染源水源时间饮用时间长于对照组,使肝癌发生的增高；饮用周边30米范围内无污染源水源、饮用深井水具有保护作用。乙肝感染是当地肝癌高发的重要危险因素,乙肝感染使肝癌发生的危险性显著升高(OR＝15.263)。肝癌家族史是肝癌发生的危险因素。经常生气、经历负性重大事件使肝癌发生的危险性越高。饮食口味清淡、多摄入薯类、辣椒、蛋类、水果具有保护作用。对三种癌症的危险因素和保护因素进行比较发现：三种癌症共同的危险因素包括分散式供水、水源周边有污染源、一级亲属肿瘤史、平常容易生气。睡眠状况差、每日饮酒、重度体力活动为食管癌、胃癌的共同危险因素。食管癌、肝癌共同危险因素包括第一次有规律吸烟年龄早于20岁、重大负性生活事件、二级亲属肿瘤史。三种癌症共同的保护因素包括水源周边无污染源、饮食口味清淡、经常吃薯类、辣椒和水果。喜食软食物、饮茶为胃癌和食管癌共同的保护因素,饮用深水井水为胃癌、肝癌共同的保护因素。结论：1.综合分析沈丘县环境卫生状况调查、农业污染与工业污染调查、病例对照研究和水样检测结果,初步可以判定工业污染、农业污染和生活污染对食管癌、胃癌、肝癌发生都有一定影响。2.在食管癌、胃癌、肝癌的发生过程中,个体行为生活方式、心理精神因素、遗传因素等仍然具有重要作用。3.对于特定致癌污染物的寻找,该研究基本显示了污染物可能的作用链条与病因链条：从污染源头迁移到区域的地表水,再由地表水渗透到饮用水,进而进入人体导致疾病和癌症。更多还原

【Abstract】 ObjectiveTo study the phenomenon of high incidence of cancer in Huaihe River Basin, Shenqiu County of Henan Province was selected as the study area. Various methods such as spatial epidemiology, ecological epidemiology, environmental epidemiology and descriptive epidemiology(case-control study) were used to investigate and evaluate historical and current condition of industrial pollution, agricultural pollution and domestic pollution of this region, to find the specific pollutants and their sources leading to water pollution and high incidence of esophageal cancer, gastric cancer and liver cancer, to evaluate the relationship between environmental factors, behavioral lifestyle factors and the three types of cancer, to explore the possible carcinogenic factors, cancer-promoting factors and protective factors, trying to build the cause-chain from pollution to cancer.Methods and Results1. Survey on agricultural pollution in Shenqiu CountyThe data on the amount of pesticides and fertilizers from1984to2005was collected in detail for descriptive analysis. The results showed the level of nitrogen surplus from1985to2005was in an upward trend in general. Since2000, the amount of nitrogen fertilizer usage in Shenqiu County has been at a higher level and reached dangerous level to some extent. Pesticide use has been at a high level, And vice versa the corresponding pollution.2. Survey on Industrial pollution in Shenqiu CountyData on the type, size, number and geographical distribution of polluting enterprises(including existing enterprises and discontinued enterprises since1985) in Shenqiu County and Shaying River upstream region was collected. The production process, types of potential pollutants and waste emissions profile was also collected. The results showed the major polluting industries of current and historical enterprises was leather, paper, chemical, printing and plastics, which discharged plenty of waste water containing various organic pollutants, heavy metals and inorganic substances, of which many are group1(carcinogenic to humans) or group2(probably or possibly carcinogenic to humans) carcinogens identified by the International Cancer Research Center (IARC).3. Survey on environmental sanitation and pollution in cluster of digestive tract cancer in Shenqiu CountySpatial hotspot exploration technology was used to distinguish the high cluster and low cluster area of digestive tract cancer in Shenqiu County, then status of environmental sanitation and environmental pollution was investigated in both high cluster and low cluster to evaluate the correlation between environmental pollution and aggregation of digestive tract cancers. The survey showed the sanitation situation of both the high cluster and low cluster was poor. Proportion of polluted rivers, ditches, ponds was high. The number of polluting industries10years ago or20years ago was significantly related with clustering of gastrointestinal cancer, of which OR values were5.932and5.218respectively.4. Detection and analysis of water samplesAccording to the results of environmental survey in Shenqiu County, water sampling spots were determined and Shaying river water, pond water, well water samples were collected. Volatile and semi-volatile organic pollutants in water samples was detected by gas chromatography-mass spectrometry detected, semi-volatile organic compounds by solid phase extraction/gas chromatography-mass spectrometry, algal toxins by HPLC.A total of390kinds of organic pollutants were detected in the water samples of Liuji through the whole spectrum analysis including228species in surface water and232species in well water, of which the peaks of dibutyl phthalate, y-sitosterol and fucose sterol in surface water and well water were significantly higher than other components, suggesting these pollutants may be the priority control pollutants of surface water and well water in this area.Environmental endocrine disruptors such as dibutyl phthalate (PAE), nonylphenol (NP), bisphenol A (BPA) were detected in the water samples. Results of Microcystin(MCs) detection showed the concentration range of MCs was among0-2.298μg/L and the average concentration of MCs in four types of water samples in the order was:river water> pond water> shallow well water> deep well water.5. Carcinogenic activity analysis of water samplesCarcinogenic activity detection of water samples was detected through the refined Balb/c3T3cell transformation methods. Results showed surface water of high contamination area in Shenqiu County is of high cell-toxic and carcinogenic activity, and the raw water has been the ability to promote cell transformation. The carcinogenicity of well water decreased with the depth increasing. After high enrichment, shallow well water less than10meters showed carcinogenic activity, while40-meter-deep well water did not show the ability to promote cell transformation.6. Case-control studyA population-based case-control study, selecting local30-70year-old patients and controls, was adopted to study the relationship between environmental factors, behavioral lifestyle factors and esophageal cancer, gastric cancer and liver cancer.Main results of esophageal cancer cases-control study:drinking time of water sources surrounded by pollution in esophageal cancer group was significantly longer than that of control group, so was decentralized water supply; history of esophageal cancer in first-class relatives or second-class relatives was a significant risk factor; social psychological factors such as negative life-events, bad sleep, easily getting angry were significantly associated with esophageal cancer. Drinking tea, light diet, partial cool and soft food, frequent intake of potatoes, pepper, garlic, nuts and fruits showed protective effect against esophageal cancer.Main results of gastric cancer case-control study:drinking time of water sources surrounded by pollution in gastric cancer group was significantly longer than that of control group, so was decentralized water supply, suggesting water sources surrounded by pollution and decentralized water supply may be risk factors for gastric cancer, whereas water sources without pollution and drinking deep-well water may be protective factors. Gastric cancer showed the characteristic of familial aggregation:history of gastric cancer in first-class relatives was significantly associated with occurrence of gastric cancer. Social psychological factors such as negative life-events, bad sleep, easily getting angry could significantly enhance the risk of gastric cancer. Drinking tea, light diet, partial soft food, frequent intake of potatoes, peppers and fruits showed protective effect against gastric cancer.Main results of liver cancer case-control study:drinking time of water sources surrounded by pollution in liver cancer group was significantly longer than that of control group, so was decentralized water supply, suggesting water sources surrounded by pollution and decentralized water supply may be risk factors for liver cancer, whereas water sources without pollution and drinking deep-well water may be protective factors. Hepatitis B infection significantly increased the risk of liver cancer (OR=15.263), suggesting hepatitis B infection was an important risk factor. Family history of liver cancer was significantly associated with liver cancer. Social psychological factors such as negative life-events, easily getting angry made the risk of liver cancer higher. Light diet, frequent intake of potato, pepper, eggs and fruits showed protective effect against liver cancer.The common risk factors and protective factors of esophageal cancer, gastric cancer and liver cancer were identified:the common risk factors of three upper gastrointestinal cancers were distributed water supply, water sources surrounded by pollution, family history of cancer among first-class relatives, easily getting angry. Poor sleep, daily alcohol consumption, severe physical activity were common risk factors of esophageal and gastric cancer. The common risk factors esophageal cance rand liver cancer were related to age of first regular smoking less than20years-old, negative life events and family history of cancer among second-class relatives. The common protective factors of three cancers included pollution-free water sources, light diet, partial soft foods, frequent intake of potatoes, peppers and fruits. Drinking tea showed protective role for gastric cancer and esophageal cancer, drinking deep-well water for gastric cancer and liver cancer.Conclusion1. Through comprehensive analysis of environmental sanitation survey, agricultural pollution and industrial pollution survey, case-control study and water detection in Shenqiu County, it was preliminary determined that industrial pollution, agricultural pollution and domestic pollution were all associated with the occurrence of esophageal cancer, gastric cancer, liver cancer.2. Lifestyle factors, social psychological factors and genetic factors still played important role in the occurrence of esophageal cancer, gastric cancer and liver cancer.3. To explore the specific cancer-causing pollutants (such as MCs), the cause-chain from pollution to cancer was build basically:source of pollution--surface water--drinking water---disease and cancer.更多还原