Perfluoroalkyl Substances (PFASs) and Liver Cancer Risk in the United States

美国的全氟烷基物质 (PFAS) 和肝癌风险

• 批准号: 10365240
• 负责人: Xuehong Zhang
• 金额: $ 81.51万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-07-01 至 2026-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10365240
• 关键词: Address; African American population; Age; Area; Biological Assay; Cancer Burden; Cancer Etiology; Cessation of life; Chemicals; Chronic Hepatitis B; Cohort Studies; Collection; Communities; Data; Diabetes Mellitus; Diagnosis; Disease; Environmental Pollution; Ethnic Origin; Ethnic group; Etiology; Evaluation; Exposure to; Follow-Up Studies; Goals; Health; Health Professional; Heavy Drinking; Hepatitis B Virus; Hepatitis C; Hepatocarcinogenesis; Hispanic Community Health Study/Study of Latinos; Hispanic Populations; Human; Incidence; Investigation; Laboratories; Laboratory Animals; Liver; Longitudinal cohort study; Malignant Neoplasms; Malignant neoplasm of liver; Measures; Metabolic Diseases; Methods; Morbidity - disease rate; Nested Case-Control Study; Not Hispanic or Latino; Nurses' Health Study; Obesity; Occupational; Occupational Exposure; Patients; Pattern; Plasma; Poly-fluoroalkyl substances; Population Heterogeneity; Prospective cohort study; Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial; Public Health; Race; Regulation; Reproducibility; Research; Resources; Risk; Risk Factors; Role; Sample Size; Sampling; Sampling Studies; Science; Smoking; Solid; Source; Technology; Tissues; United States; Viral; Virus; Virus Diseases; Weight Gain; Women' s Health; Work; base; cancer health disparity; cancer risk; cancer subtypes; carcinogenicity; cohort; design; experience; exposed human population; health disparity; high risk; improved; innovation; insight; liver cancer prevention; men' s group; mortality; novel; perfluorooctane sulfonate; perfluorooctanoic acid; preventive intervention; prospective; racial and ethnic; racial diversity; sex; stem

Project Summary/Abstract Liver cancer is one of the most rapidly increasing cancers over the past decades in the United States. The causes for this long-term increase are unclear, but could stem from exposures to possibly carcinogenic environmental contaminants. One likely source is per- and polyfluoroalkyl substances (PFAS), a group of synthetic chemicals that are highly persistent and accumulate in human liver tissue. Emerging, converging evidence from laboratory animals and occupational mortality studies strongly support the role of PFAS in liver carcinogenesis. However, these studies are limited by small sample sizes, restriction to occupational exposure, and studying single types of PFAS. Hence, we propose the first comprehensive prospective pooled cohort study in non-occupational settings to examine real-world human exposure to PFAS (of multiple types and mixtures) in relation to liver cancer incidence. Our long-term goal is to identify novel risk factors for liver cancer to reduce liver cancer burden. Moreover, liver cancer incidence is higher in African Americans and Hispanics compared with whites, but the causes of these disparities remain unclear. Furthermore, more liver cancer cases in the United States are not caused by chronic hepatitis B virus (HBV) and C virus (HCV) infections, but risk factors for non-viral liver cancer remain poorly understood. The objective of this proposal is to comprehensively assess the relationship between mixture exposure to PFAS and liver cancer risk overall, by racial/ethnic groups, and by HBV/HCV status. To do so, we propose this first comprehensive study to date of exposures to PFAS and liver cancer risk through a pooling project that leverages extensive resources from six well-characterized cohort studies. This pooling project includes a racially/ethnically diverse population followed for up to 32 years, along with pre-diagnosis plasma samples and validated covariate data. Our specific aims are to characterize the associations between plasma levels of PFAS and risk of developing liver cancer in this pooled nested case-control study with measured HBV/HCV status data (Aim 1); and assess the extent to which certain PFAS mixture patterns act synergistically to increase liver cancer risk (Aim 2). In exploratory aims, we will quantify the aforementioned associations by major liver cancer subtypes, and further estimate the associations between plasma PFAS levels and survival among patients with liver cancer. This proposal is innovative in addressing an important, yet understudied research area of PFAS and liver cancer through integrating cutting-edge technologies of PFAS assays and advanced methods of mixture analyses into longitudinal cohort studies. The contribution is significant because this research will generate new insights into the etiology of liver cancer, enable design of new prevention/intervention strategies and actions that reduce liver cancer morbidity and mortality and related disparities. These findings will also provide new information on health effects of PFAS for practitioners and regulatory agencies to make solid decisions, regulations, and action plans to improve public health.

项目摘要/摘要 肝癌是过去几十年来最快增加的癌症之一。这 长期增加的原因尚不清楚，但可能源于可能是致癌的暴露 环境污染物。一种可能的来源是每组和多氟烷基物质（PFA），一组 高度持久且积聚在人肝组织中的合成化学物质。新兴，融合 实验动物和职业死亡率研究的证据强烈支持PFA在肝脏中的作用 致癌作用。但是，这些研究受到小样本量的限制，限制了职业 暴露和研究单一类型的PFA。因此，我们提出了第一个全面的预期汇总 在非职业环境中研究的队列研究，以检查现实世界中的人类接触PFA（多种类型 和混合物）与肝癌的发生有关。我们的长期目标是确定肝脏的新风险因素 减轻肝癌负担的癌症。此外，非裔美国人的肝癌发病率更高， 与白人相比，西班牙裔人，但这些差异的原因尚不清楚。此外，更多的肝脏 美国的癌症病例不是由慢性丙型肝炎病毒（HBV）和C病毒（HCV）引起的 感染，但非病毒肝癌的危险因素仍然了解不足。该提议的目的是 全面评估混合物暴露于PFA和肝癌风险总体之间的关系， 由种族/族裔群体以及HBV/HCV身份。为此，我们提出了这项首次全面研究 通过一个利用大量资源的合并项目，对PFA和肝癌风险的暴露日期 从六项良好的队列研究中。这个合并项目包括种族/种族多元化的人口 紧随其后的是32年，以及诊断前血浆样品并验证了协变量数据。我们的 具体目的是表征PFA的血浆水平与发展肝脏的风险之间的关联 在这项合并的嵌套病例对照研究中，使用测量的HBV/HCV状态数据（AIM 1）；并评估 某些PFAS混合模式协同起作用以增加肝癌风险的程度（AIM 2）。在 探索目的，我们将通过主要的肝癌亚型量化上述关联，并进一步量化 估计血浆PFA水平与肝癌患者的存活之间的关联。这 提案在解决PFA和肝癌的重要而研究的研究领域方面具有创新性 通过整合PFAS分析的尖端技术和混合分析的高级方法 纵向队列研究。贡献很重要，因为这项研究将产生新的见解 肝癌的病因，实现新的预防/干预策略以及减少的行动 肝癌发病率和死亡率以及相关差异。这些发现还将提供有关的新信息 PFA对从业者和监管机构做出可靠的决定，法规和法规机构的健康影响 行动计划改善公共卫生。