The 10,000 Families Cohort: a new study to understand the environmental causes of cancer

摘要 10,000个家庭研究(10KFS)将是在明尼苏达州进行的一项新的基于家庭的队列研究，明尼苏达州是10,000人的土地 湖边的。由于我们血液系统恶性肿瘤(白血病、淋巴瘤和骨髓增生异常)的高发病率 综合症)，我们将把我们的建议集中在可能是血液病的令人担忧的环境暴露上 国际癌症研究机构定义的人类体内证据有限的致癌物 (IARC)。这包括草甘膦、多氟烷基物质(PFAS)和氡，所有这些物质都有 明尼苏达州流行率的地理差异被描述得很好。在UG3阶段，我们将 评估创新的暴露评估方法，并招募不同的参与者加入10KFS 一群人。暴露评估将包括居住历史、空气中的环境测量和目前的水中。 居住，以及通过硅胶可穿戴手镯、血清、头发和 尿液。参与者将从目标县招募，这些县将最大限度地将暴露于我们的三个县 致癌物质，包括农村和移民社区中代表性不足的人群。我们 将测量不确定潜能的克隆性造血(CHIP)，这是血红素恶性的前兆，以及 免疫和表观遗传学的扰动是我们在UH3阶段与癌症相关的主要结果。我们的 目标是从4,000个家庭招募8,750名参与者，使用以下招聘战略 已经开发并进行了试点测试。我们的中心假设是全氟辛烷磺酸、草甘膦和氡对 在明尼苏达州，血液恶性肿瘤和癌症发病率普遍增加。癌症发病率 将通过与明尼苏达州癌症报告系统(MCRS)和 虚拟汇集登记癌症链接系统。UG3阶段的科学目标将是：1)评估 易于大规模实施的全氟辛烷磺酸和草甘膦的创新暴露评估方法 规模研究和2)描述代表性不足的移民人口的暴露负担。我们会 在UH3阶段完成对研究人群的招募，具体目标是：1)确定 氡、草甘膦和全氟辛烷磺酸水平是否与CHIP和2的患病率增加有关 利用表观基因组学检验氡、草甘膦和全氟辛烷磺酸暴露与 免疫失调和表观遗传特征。我们的社区参与将以伙伴关系进行 与非营利性研究机构合作，通过研究促进拉美裔倡导和社区赋权 (Hacer)、明尼苏达共济会和东方之星勋章以及来自 家庭发展推广中心。这项研究的结果将提供必要的数据，以告知 这些药物是血液致癌物质，它将解决记录在案的暴露于 我们的州，并提供关于这些接触和教育的社区外展和教育机制 任何潜在的癌症联系。

Abstract The 10,000 Families Study (10KFS) will be a new, family-based cohort study in Minnesota, the ‘Land of 10,000 Lakes’. Due to our high incidence rates of hematologic malignancy (leukemia, lymphoma, and myelodysplastic syndromes), we will focus our proposal on environmental exposures of concern that are possible hematologic carcinogens with limited evidence in humans as defined by the International Agency for Research on Cancer (IARC). This includes glyphosate, poly- and perfluoroalkyl substances (PFAS), and radon, all of which have well-described geographic variation in prevalence in the state of Minnesota. During the UG3 phase, we will evaluate innovative exposure assessment methodologies and recruit diverse participants into the 10KFS cohort. Exposure assessment will include residential history, ambient measures in air and water at current residence, as well as individual-level exposure assessed with silicone wearable bracelets, serum, hair, and urine. Participants will be recruited from targeted counties that maximize the exposure distribution to our three carcinogens of interest and include under-represented populations from rural and immigrant communities. We will measure clonal hematopoiesis of indeterminate potential (CHIP), a precursor to heme malignancy, and perturbations in immunity and epigenetics as our primary cancer-related outcomes in the UH3 phase. Our target is to recruit 8,750 participants from 4,000 households to participate using recruitment strategies that have been developed and pilot tested. Our central hypothesis is that PFAS, glyphosate and radon contribute to increased hematologic malignancy specifically, and cancer incidence broadly, in Minnesota. Cancer incidence will be determined via annual record linkage with the Minnesota Cancer Reporting System (MCRS) and the Virtual Pooled Registry Cancer Linkage System. The scientific aims in the UG3 phase will be to: 1) evaluate innovative exposure assessment methods for PFAS and glyphosate that can be easily implemented in a large scale study and 2) describe the exposure burden in under-represented immigrant populations. We will complete recruitment of the study population in the UH3 phase where the specific aims are to: 1) determine whether levels of radon, glyphosate, and PFAS are associated with increased prevalence of CHIP and 2) utilize epigenomics to test the hypotheses that radon, glyphosate and PFAS exposure are associated with immune dysregulation and epigenetic signatures. Our community engagement will be conducted in partnership with the non-profit research institute Hispanic Advocacy and Community Empowerment Through Research (HACER), the Minnesota Freemasons and Order of the Eastern Star and community educators from the Extension Center for Family Development. The results of this study will provide needed data to inform whether these agents are hematologic carcinogens, it will address documented disparities in exposure that occur within our state and provide a mechanism for community outreach and education concerning these exposures and any potential cancer link.