Perfluoroalkyl substances and risk of kidney cancer in US men and women

全氟烷基物质与美国男性和女性患肾癌的风险

• 批准号: 10584037
• 负责人: LOREN LIPWORTH
• 金额: $ 71.75万
• 依托单位: BROWN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-06-20 至 2027-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10584037
• 关键词: Air; Black race; Blood; Case/Control Studies; Chemical Structure; Clear cell renal cell carcinoma; Cohort Studies; Communities; Community Health; Data; Development; Diabetes Mellitus; Diagnosis; Diagnostic; Environment; Environmental Exposure; Ethnic Origin; Exposure to; Follow-Up Studies; Food Contamination; General Population; Health; Health Hazards; Health Professional; Hearing; Hispanic; Hispanic Community Health Study/Study of Latinos; Histologic; Human; Hypertension; Incidence; Individual; Industrial Product; Industrialization; Intake; Isomerism; Kidney; Knowledge; Length; Malignant - descriptor; Measurement; Measures; Medical; National Institute of Environmental Health Sciences; Nested Case-Control Study; Nurses' Health Study; Obesity; Observational Study; Occupational; Organ; Parents; Participant; Pattern; Physicians; Plasma; Poly-fluoroalkyl substances; Population; Population Study; Process; Production; Prospective Studies; Prospective cohort; Prospective, cohort study; Public Health; Race; Regulation; Renal Cell Carcinoma; Renal carcinoma; Research; Resistance; Resources; Risk; Risk Factors; Sampling; Science; Serum; Smoking; Testing; Time; United States Environmental Protection Agency; Water; Woman; Work; bioaccumulation; cancer risk; cohort; comorbidity; computerized; consumer product; dermal exposure; drinking water; ethnic disparity; experience; experimental study; exposed human population; man; men; mortality; perfluorooctane sulfonate; perfluorooctanoic acid; pollutant; population based; prospective; racial disparity; racial diversity; renal damage; response; sound; tumor; urologic

Abstract PFAS are a class of man-made organofluorine compounds whose presence in the environment is an emerging, worldwide public health concern and a priority in environmental and human health research. Many PFAS are environmentally persistent, bioaccumulative, and have long half-lives in humans. Of particular concern is that environmental exposure to PFAS may increase the risk of kidney cancer, whose incidence has shown unexplained sustained and rapid increases in the US during the past decades. Several lines of emerging evidence strongly support that PFAS exposures may increase the risk of kidney cancer among humans: First, the kidney is a target organ of PFAS, which cause serious damage to the kidney at the levels commonly experienced by US population; Second, PFAS exposures have been associated with kidney damage that is known to increase kidney cancer risk; Third, a recent population-based case-control study of 324 RCC cases and 324 controls from NCI supports the findings of early occupational mortality studies that PFAS exposure increases kidney cancer risk. Much larger prospective studies of diverse, non-occupationally exposed populations are urgently needed to either confirm or refute these preliminary findings. Here, we propose a prospective nested case-control study to test the association between PFAS exposure and renal cell carcinoma (RCC, more than 85% of all cases of kidney cancer). We will utilize the extensive resources from five large and well-characterized US prospective cohorts: The Southern Community Cohort Study; Hispanic Community Health Study/Study of Latinos Cohort; Nurses’ Health Study; Health Professionals Follow-Up Study; and Physicians' Health Study. We will measure pre-diagnostic plasma levels of 40 PFAS from ~650 incident RCC cases and their individually matched controls (~1,300 controls in 1:2 ratio). Specifically, we will examine the following hypotheses: 1. Environmental exposure to PFAS increases the risk of RCC. In particular, environmental exposure to PFOA, PFOS and PFHxS increases RCC risk; 2. Risk of RCC associated with environmental PFAS exposure varies by mixture patterns, and varies by PFAS chemical structure, branched vs linear isomers, and short vs. long chain length; and 3. Established baseline risk factors of RCC (hypertension, obesity, diabetes and smoking) moderate the relationship between PFAS exposure and risk of RCC. In exploratory aims, we will test if the risk of RCC associated with individual PFAS exposures varies by histologic type of RCC or by race, and thus may contribute to racial disparities in kidney cancer risk. This proposed study fills a critical knowledge gap and represents the first large prospective cohort study to investigate the alleged association between PFAS exposure and kidney cancer risk in the US among diverse cohorts of non-occupationally exposed individuals. The results of the study will inform the medical and public health communities about the potential health effects of PFAS exposure and can help regulators make sound, science-based decisions.

摘要 PFAS 是一类人造有机氟化合物，其在环境中的存在是 新兴的全球公共卫生问题以及环境和人类健康研究的优先事项。许多 PFAS 具有环境持久性、生物累积性，并且在人体中具有较长的半衰期。特别值得关注 环境暴露于 PFAS 可能会增加患肾癌的风险，其发病率已表明 过去几十年来美国出现无法解释的持续快速增长。新兴的几条线 有证据有力地证明，接触 PFAS 可能会增加人类患肾癌的风险：首先， 肾脏是PFAS的靶器官，PFAS通常在以下水平对肾脏造成严重损害： 美国民众所经历的；其次，PFAS 暴露与肾脏损伤有关，即 已知会增加肾癌风险；三、最近一项针对 324 例 RCC 病例的基于人群的病例对照研究 和来自 NCI 的 324 名对照支持早期职业死亡率研究的结果，即 PFAS 暴露 增加肾癌风险。对不同的、非职业暴露的更大规模的前瞻性研究 迫切需要人们证实或反驳这些初步调查结果。 在这里，我们提出了一项前瞻性巢式病例对照研究来测试 PFAS 暴露与 肾细胞癌（RCC，占所有肾癌病例的 85% 以上）。我们将利用广泛的资源 来自五个大型且特征明确的美国前瞻性队列：南方社区队列研究； 西班牙裔 社区健康研究/拉丁裔群体研究； 护士健康研究；卫生专业人员跟踪研究； 和医生健康研究。我们将测量约 650 起事件中 40 种 PFAS 的诊断前血浆水平 RCC 病例及其单独匹配的对照（约 1,300 个对照，比例为 1:2）。具体来说，我们将检查 以下假设： 1. 环境中暴露于 PFAS 会增加 RCC 的风险。尤其， 环境中暴露于 PFOA、PFOS 和 PFHxS 会增加 RCC 风险； 2. 相关的肾细胞癌风险 环境中 PFAS 暴露量因混合物模式和 PFAS 化学结构而异， 支链异构体与直链异构体，以及短链与长链长度； 3. 建立基线风险因素 RCC（高血压、肥胖、糖尿病和吸烟）调节 PFAS 暴露之间的关系 和 RCC 的风险。在探索性目标中，我们将测试 RCC 风险是否与个体 PFAS 相关 暴露因肾细胞癌的组织学类型或种族而异，因此可能会导致种族差异 肾癌风险。这项拟议的研究填补了一个关键的知识空白，代表了第一个大型前瞻性研究 队列研究旨在调查美国 PFAS 暴露与肾癌风险之间所谓的关联 在非职业暴露个体的不同群体中。研究结果将告知医学界 和公共卫生界了解 PFAS 暴露对健康的潜在影响，并可以帮助监管机构制定 合理、基于科学的决策。