The Effect of Aflatoxin Regulation on Global Liver Cancer Risk

描述（由申请人提供）：本EUREKA申请的目的是开发一种多因素建模工具，可以为决策者提供有关如何制定食源性黄曲霉毒素标准以降低全球肝癌发病率的信息。肝癌（肝细胞癌）是全球癌症死亡的第三大原因，其发病率的上升与慢性乙型肝炎（HBV）和丙型肝炎（HCV）感染的上升相当。黄曲霉毒素是一种强效的肝癌原，与乙型肝炎病毒和丙型肝炎病毒协同作用，产生的肝癌风险比单独接触任何一种高30倍。黄曲霉毒素是在温暖的气候条件下由玉米和花生中的黄曲霉和寄生蜂产生的。因此，在控制黄曲霉毒素资源匮乏的热带和亚热带欠发达国家，全球最易患黄曲霉毒素引起的肝癌的人群是那些食用高水平玉米和花生的人。我们假设，模拟公共卫生影响和贸易/经济后果的计算模型可以为监管标准如何减轻全球癌症负担提供独特的见解。100多个国家制定了食品中黄曲霉毒素的最高允许含量标准。这些标准因国而异。目前正在努力协调全球黄曲霉毒素标准，以防止世界粮食贸易争端。我们讨论的问题是：为了最好地保护全球健康，统一的黄曲霉毒素标准应该是什么？具有讽刺意味的是，设定一个非常严格的标准可能会导致更多的癌症病例，原因有三：1。富裕的粮食进口国由于肝炎流行率低，其保健效益有限，而粮食出口最不发达国家为达到这些标准可能会产生过高的成本。2. 限制粮食出口市场可能会加剧最不发达国家的贫困，从而加剧饥饿和健康状况不佳，从而增加肝炎感染和肝癌的风险。3. 为了保护其出口市场，亚洲和非洲国家可能会尝试出口其质量最好的食品，并将污染最严重的食品留在国内，这增加了世界上目前肝炎感染率最高的部分地区消费黄曲霉毒素和肝癌的风险。由于进行临床试验既不实际也不符合伦理，而且回顾性数据有限，因此计算机模拟建模是一种非常有用的技术，可以检查全球不同黄曲霉毒素标准对食品贸易和癌症发病率的影响。公共卫生决策分析方法的一个强大属性是能够同时评估几个维度。我们试图创建一种创新的建模工具，将全球肝癌和肝炎发病率、玉米和坚果中的黄曲霉毒素暴露、成本和技术变化整合到一个单一的决策分析框架中。我们的具体目标是确定在当前条件和未来情景下，选定的黄曲霉毒素统一标准对全球食品出口损失和全球黄曲霉毒素引起的肝癌负担的影响。

DESCRIPTION (provided by applicant): The purpose of this EUREKA application is to develop a multi-factorial modeling tool that can provide decision- makers information on how to set foodborne aflatoxin standards that reduce global liver cancer incidence. Liver cancer (hepatocellular carcinoma) is the 3rd-leading cause of cancer deaths worldwide, with an increasing incidence that parallels the rise in chronic hepatitis B (HBV) and hepatitis C (HCV) infection. Aflatoxin is a potent hepatocarcinogen that synergizes with HBV and HCV to produce 30-fold higher liver cancer risk than either exposure alone. Aflatoxin is produced by the fungi Aspergillus flavus and A. parasiticus in maize and peanuts under warm climatic conditions. Hence, the global populations most at risk of aflatoxin-induced liver cancer are those who consume high levels of maize and peanuts, in less developed countries (LDCs) in the tropics and subtropics where resources to control aflatoxin are scarce. We hypothesize that computational modeling that simulates both public health effects and trade / economic consequences can provide unique insights into how regulatory standards can ameliorate global cancer burden. Over 100 nations have set standards on maximum allowable aflatoxin levels in food. These standards vary widely from nation to nation. Efforts are now being made to harmonize aflatoxin standards globally, to prevent world food trade disputes. We address the question: What should the harmonized aflatoxin standard be to best protect global health? Ironically, setting a very strict standard could result in more cancer cases, for 3 reasons: 1. Rich, food-importing countries would have limited health benefits because of low hepatitis prevalence, while food-exporting LDCs may incur excessive costs to meet such standards. 2. Limiting food export markets could increase poverty in LDCs, which would augment hunger and poor health conducive to increased hepatitis infection and liver cancer risk. 3. To preserve their export markets, Asian and African nations may attempt to export their best-quality food and keep the most highly contaminated food domestically, raising the risk of aflatoxin consumption and liver cancer in parts of the world that currently have the highest rates of hepatitis infection. Because conducting clinical trials is neither practical nor ethical, and retrospective data are limited, computer simulation modeling is an extremely useful technique to examine the consequences of different global aflatoxin standards on food trade and cancer incidence. A powerful attribute of the decision analytic approach to public health is the ability to evaluate several dimensions simultaneously. We seek to create an innovative modeling tool that integrates global liver cancer and hepatitis incidence, aflatoxin exposure through maize and nuts, costs, and technological changes into a single decision-analytic framework. Our specific aim is to determine the effect of selected harmonized aflatoxin standards on both global food export losses and global burden of aflatoxin-induced liver cancer, under current conditions and future scenarios. PUBLIC HEALTH RELEVANCE: Public Health Relevance Statement: As befits the purpose of EUREKA, our proposed research accelerates knowledge in a crucial time when the United Nations and the World Trade Organization are pushing to harmonize food safety standards across nations. Until now, little work has been done to assess global health impacts of harmonized standards; now, we are in a position to apply novel modeling techniques to provide that necessary knowledge to decision-makers. While we focus on the impact of a harmonized aflatoxin standard on global liver cancer burden, the methodologies can be broadened to address standard-setting of other important carcinogens.