基于社区人群队列的五氯酚长期环境污染与肿瘤发病风险研究

Pentachlorophenol (PCP) has been widely used for killing snails in area of China where schistosomiasis is epidemic. Given long term using PCP in the natural environment can generate accumulation in the animals and plants, finally and continuingly be absorbed by humans through biological chain. Considering the potential health risks of PCP, China restricted the production and use of PCP. However the contaminant state and human burden of PCP had high levels. With the re-emergence of schistosomiasis in the traditional epidemic areas and using for fish pond cleaning, the production and use PCP for snail elimination and schistosomia control has increased again. The increased PCP use likely has resulted in more environmental contamination and potential health risks. Our previous study show that long-term environmental PCP exposure can increase the standardized incidence rates of all cancer sites, especially for some specific cancers related to PCP exposure in some schistosomiasis epidemic areas. PCP levels in drinking water were also high. It was testified that exposed to PCP can increase the risk of cancer by animal experiments in some countries. But no systematic examination of the PCP contamination in China has been conducted, and the carcinogenicity to human was uncertain based on population studies. The current study will conduct a population-based study on the relationship between long-term environment PCP exposure and cancer risk. Firstly, to collect cancer incidence and death cases by cancer and health registry system, and explore the spectrum of cancer and induction period in long-term exposure areas. Secondly, to examine the contamination status and human burden of PCP and at the same time we will analyze other risk factors of cancers. By conduct prospective cohort studies, ecological studies and case-cohort study to systematically evaluate the relationship between long-term and low-level environmental PCP exposure and cancer risk. So, this study will provide important reference of assessing the toxicity of PCP, and establish environmental health standards.

五氯酚（PCP）曾作为灭螺剂，被广泛用于控制血吸虫在疫区的流行传播，最新研究表明我国环境与人体的负荷长期保持较高的暴露水平。近年来，由于血吸虫复燃及水产养殖业清塘需要，PCP被大范围违禁使用，导致环境污染的进一步加重。我们前期研究发现PCP长期污染区人群肿瘤高发，饮用水中PCP含量较高。虽然动物实验已证实PCP具有致肿瘤性，但其长期环境污染与社区人群肿瘤发病风险性的关系还未得到揭示。本课题拟通过PCP长期污染区环境及人体中的暴露水平和历史投放数据，基于社区人群队列，运用前瞻性追踪研究、病例队列研究和生态学研究等方法系统地分析PCP污染区各类型肿瘤的发病状况及其影响因素；探讨PCP污染区的肿瘤谱及特异性肿瘤的潜隐期；较全面地了解PCP的暴露水平和污染现状；在控制其他环境化合物等潜在混杂因素影响下，评价PCP长期环境污染的肿瘤发病风险性，为PCP的毒性评价及相关环境卫生标准制定提供理论依据。

五氯酚（pentachlorophenol，PCP）曾作为灭螺剂，被广泛用于控制血吸虫在疫区的流行传播。本项目基于PCP历史投放区，通过PCP历史投放数据、环境和人体的PCP检测数据，运用流行病学方法较全面地了解环境和人体的PCP暴露水平及其与肿瘤发病风险的关系。项目研究结果：1.建立了固相萃取-气相色谱串联质谱（SPE-GC/MS/MS）检测饮用水及液液萃取-气相色谱串联质谱（LLE-GC/MS/MS）检测人体标本氯酚类化合物的方法。2. PCP污染区，环境和人体中PCP暴露水平较高。76个抽样点的饮用水的水源水和末梢水均检测出五氯酚，水源水PCP平均浓度为56.97ng/L，中位数为16.76ng/L，范围为3.90~684.00ng/L。PCP暴露区自然人群尿液中PCP含量在0~485.99ug/L，其中高暴露地区平均浓度达30.46ug/L，而低暴露地区仅为0.26ug/L。3. 我国PCP暴露区人群具有与PCP职业人群不同的接触途径和接触时间，存在着不同的恶性肿瘤谱，肿瘤标化发病率顺位前十依次为胃癌、气管支气管肺癌、结直肠癌、食管癌、肝癌、乳腺癌、胆囊癌、胰腺癌、子宫颈癌、脑神经系统癌。4. PCP长期低剂量环境污染可以诱发社区人群肿瘤的高发。PCP历史投放量与恶性肿瘤的发病率呈正相关，当PCP暴露年限大于10年时，恶性淋巴瘤、白血病、胃癌、食管癌、膀胱癌的发病风险较高。以环境中PCP低暴露区为参照组，PCP中暴露可能增加社区自然人群的淋巴癌（SRR=6.16）、膀胱癌（SRR=1.96）、结直肠癌（SRR=1.51）、甲状腺癌（SRR=1.49）、肝癌（SRR=1.37）等发病风险；高暴露可能增加了淋巴瘤（SRR=19.44）、白血病（SRR=17.24）、膀胱癌（SRR=3.46）、胰腺癌（SRR=3.41）、肝癌（SRR=3.31）等肿瘤的发病风险性。PCP暴露时间越长，特异性肿瘤发病率越高。5.建全了沿江流域的肿瘤监测社区，初步建立了社区自然人群队列和PCP特异性肿瘤标本库，收集肿瘤病人的基本信息，分析PCP与其他环境及遗传因素的联合作用。本项目探讨了长期低剂量五氯酚环境污染的肿瘤发病风险性及特异性肿瘤谱，为五氯酚的致癌性评价及污染区的肿瘤预防控制提供了理论依据；建立的社区人群队列和肿瘤标本库将会推进皖江地区环境污染与肿瘤发病风险研究的进一步研究。