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.

摘要全氟化合物是一类人工合成的有机氟化合物，其在环境中的存在是一种 新出现的全球公共卫生问题，是环境和人类健康研究的优先事项。许多 全氟辛烷磺酸具有环境持久性、生物蓄积性和较长的人体半衰期。特别令人担忧 在环境中暴露于全氟辛烷磺酸可能会增加患肾癌的风险，其发病率已显示 在过去的几十年里，美国出现了无法解释的持续快速增长。新出现的几条线路 有强有力的证据表明，接触PFAS可能会增加人类患肾癌的风险：首先， 肾是PFAS的靶器官，通常会在各个层面对肾脏造成严重的损害。 第二，接触全氟辛烷磺酸与肾脏损害有关，即 已知会增加肾癌风险；第三，最近一项针对324例肾癌病例的基于人群的病例对照研究 来自NCI的324名控制组支持了早期职业死亡率研究的结果，即接触PFAS 会增加患肾癌的风险。对不同的、非职业暴露的更大规模的前瞻性研究 迫切需要民众来证实或驳斥这些初步发现。 在这里，我们提出了一项前瞻性的嵌套病例对照研究，以检验全氟辛烷磺酸暴露与 肾细胞癌(肾癌，占所有肾癌病例的85%以上)。我们将利用广泛的资源 来自五个大的和特征良好的美国预期队列：南方社区队列研究； 西语裔 社区健康研究/拉丁裔队列研究； 护士健康研究；卫生专业人员随访研究； 和医生健康研究。我们将测量~650起事件中40个PFA的诊断前血浆水平 肾癌患者及其各自配对的对照组(约1300名对照组，比例为1：2)。具体来说，我们将审查 以下假设：1.环境暴露于全氟辛烷磺酸会增加肾癌的风险。特别是， 环境暴露于全氟辛烷磺酸、全氟辛烷磺酸和全氟辛烷磺酸会增加肾细胞癌的风险；2.肾细胞癌的风险与 环境中全氟辛烷磺酸的暴露因混合物模式而异，并因全氟辛烷磺酸的化学结构而异， 支链异构体与直链异构体，以及短链长与长链长；以及3.已确定的基线风险因素 RCC(高血压、肥胖、糖尿病和吸烟)缓和了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的风险是否与单个PFAS相关 暴露因肾癌的组织学类型或种族而异，因此可能导致 患肾癌的风险。这项拟议的研究填补了一个关键的知识空白，并代表了第一个大的前瞻性研究 一项队列研究，旨在调查美国PFAS暴露与肾癌风险之间的所谓关联 在不同的非职业性接触人群中。这项研究的结果将通知医务人员 和公共卫生界关于接触全氟辛烷磺酸对健康的潜在影响，并可以帮助监管机构制定 合理、以科学为基础的决策。