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: 10652966
• 负责人: Xuehong Zhang
• 金额: $ 70.44万
• 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/10652966
• 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; Disparity; Environmental Pollutants; Ethnic Origin; Ethnic Population; 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; Intervention; 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; Orthohepadnavirus; Patients; Pattern; Plasma; Policy Maker; Poly-fluoroalkyl substances; Population; Population Heterogeneity; Prevention; Prevention strategy; 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; cancer health disparity; cancer risk; cancer subtypes; carcinogenicity; cohort; design; diabetes risk; ethnic diversity; experience; exposed human population; health disparity; high risk; improved; innovation; insight; liver cancer prevention; manufacture; men' s group; mortality; novel; perfluorooctane sulfonate; perfluorooctanoic acid; prospective; racial diversity; racial population; 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.

项目总结/摘要 肝癌是美国过去几十年来增长最快的癌症之一。的 这种长期增加的原因尚不清楚，但可能源于暴露于可能致癌的环境中。 环境污染物。一个可能的来源是全氟烷基和多氟烷基物质（PFAS），一组 高持久性的合成化学物质，并在人体肝脏组织中积累。新兴，融合 来自实验室动物和职业死亡率研究的证据强烈支持PFAS在肝脏中的作用。 致癌作用然而，这些研究受到样本量小，职业限制， 暴露，并研究单一类型的PFAS。因此，我们提出了第一个全面的前瞻性汇集 在非职业环境中进行的队列研究，以检查现实世界中人类对PFAS的暴露（多种类型 和混合物）与肝癌发病率的关系。我们的长期目标是确定肝脏疾病的新风险因素。 降低肝癌负担。此外，非裔美国人的肝癌发病率较高， 西班牙裔与白人相比，但这些差异的原因仍然不清楚。此外，更多的肝脏 美国的癌症病例不是由慢性B型肝炎病毒（HBV）和丙型肝炎病毒（HCV）引起的 感染，但非病毒性肝癌的风险因素仍然知之甚少。本提案的目的是 为了全面评估PFAS混合物暴露与肝癌风险之间的关系， 按种族/民族和HBV/HCV状态分类。为此，我们建议进行第一次全面研究， 通过利用广泛资源的汇集项目，确定PFAS暴露日期和肝癌风险 来自六个特征良好的队列研究。这个汇集项目包括种族/族裔多样化的人口 随访长达32年，以及诊断前血浆样本和经验证的协变量数据。我们 具体的目的是描述PFAS血浆水平与肝脏疾病风险之间的关系， 在这项混合巢式病例对照研究中，使用测量的HBV/HCV状态数据（目标1）评估癌症; 某些PFAS混合模式协同作用增加肝癌风险的程度（目标2）。在 为了探索性的目的，我们将量化主要肝癌亚型的上述相关性，并进一步 评估血浆PFAS水平与肝癌患者生存率之间的关系。这 该提案在解决PFAS和肝癌这一重要但研究不足的研究领域方面具有创新性 通过将PFAS检测的尖端技术和混合物分析的先进方法整合到 纵向队列研究。这一贡献是重大的，因为这项研究将产生新的见解， 肝癌的病因，使设计新的预防/干预战略和行动， 肝癌发病率和死亡率及相关差异。这些发现还将提供新的信息， PFAS对从业人员和监管机构的健康影响，以做出可靠的决策，法规， 改善公共卫生的行动计划。

项目成果

Association of per- and polyfluoroalkyl substance exposure with fatty liver disease risk in US adults.

• DOI: 10.1016/j.jhepr.2023.100694
• 发表时间: 2023-05
• 期刊: JHEP REPORTS
• 影响因子: 8.3
• 作者: Zhang, Xinyuan;Zhao, Longgang;Ducatman, Alan;Deng, Chuanjie;von Stackelberg, Katherine Ellen;Danford, Christopher J.;Zhang, Xuehong
• 通讯作者: Zhang, Xuehong