Modeling multiple environmental exposures and childhood leukemia risk

模拟多种环境暴露和儿童白血病风险

基本信息

批准号：
10078942
负责人：
David Charles Wheeler
金额：
$ 18.6万
依托单位：
VIRGINIA COMMONWEALTH UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-01-01 至 2022-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10078942
关键词：
Accounting Area California Carpet Case-Control Studies Chemical Exposure Chemical Models Chemicals Child Childhood Leukemia Complex County Data Development Dust Enrollment Environmental Epidemiology Environmental Exposure Environmental Risk Factor Epidemiology Etiology Evaluation Exposure to Goals Hand Health House Dust Household Incidence Income Individual Ingestion Lead Malignant Neoplasms Measures Methodology Methods Modeling Neighborhoods Oral cavity Outcomes Research Polychlorinated Biphenyls Population Study Public Health Publishing Research Residual state Risk Risk Assessment Risk Factors San Francisco Socioeconomic Status Statistical Methods Structure Sum Time Time Study Uncertainty United States Work cancer risk chemical group detection limit environment related cancer environmental chemical environmental chemical exposure epidemiology study exposure route indexing insight novel novel strategies simulation socioeconomics

项目摘要

Incidence for many cancers is suspected to be associated with chemicals through environmental routes of exposure. Individuals are exposed to a large number of diverse environmental chemicals simultaneously and evaluation of multiple chemical exposures is important for identifying cancer risk factors. Increasingly, exposures are being measured for a large number of chemicals in epidemiologic studies to allow for a more comprehensive assessment of cancer risk factors in the exposome. However, most existing studies of environmental chemical exposures and cancer use a single-chemical approach that evaluates chemicals independently as risk factors. Traditional statistical methods used in existing studies are significantly challenged by the typically strong correlation observed among many environmental chemical exposures, as well as other environmental and socioeconomic variables. There is a need for development and assessment of statistical methods to model environmental cancer risk that consider a large number of diverse chemicals with different effects for different chemical classes. The specific aims of this research are 1) to develop more comprehensive exposure risk models and apply them to a case-control study of childhood leukemia in California that contains concentrations measured for a large number of diverse chemicals, 2) to account for uncertainty associated with imputing chemical concentrations below the limit of detection when estimating chemical mixture effect, and 3) to account for neighborhood socioeconomic status and residual confounding when estimating chemical exposure effects. The study of childhood leukemia will benefit from environmental chemical risk analysis because it is a cancer with an unclear etiology and established risk factors that account for only a small proportion of the total annual cases in the United States. The expected outcomes of this research will be 1) new statistical approaches to model environmental cancer risk that consider environmental exposures more comprehensively while also accounting for uncertainty related to missing data, and 2) an evaluation of the effects of exposure to chemicals from many chemical classes and an identification of the important chemicals for childhood leukemia. The significance of this research is two-fold. First, the development and evaluation of new statistical approaches to risk analysis that consider multiple diverse environmental exposures while accounting for uncertainty will advance the field of environmental epidemiology research. Second, this will be the first environmental risk analysis of a case-control study of childhood leukemia that estimates effects for different chemical classes using a large number of correlated chemical exposures while also adjusting for known demographic risk factors at the household and neighborhood level and accounting for uncertainty related to missing data. The methodological approaches developed in this work will be applicable to many other cancers associated with multiple environmental exposures of differing types.

怀疑许多癌症的发病率与化学物质通过环境路线相关接触。个人同时接触大量不同的环境化学物质评估多种化学暴露对于鉴定癌症危险因素很重要。日益，在流行病学研究中，正在为大量化学物质测量暴露，以允许更多全面评估exposome中的癌症危险因素。但是，大多数现有的研究环境化学暴露和癌症使用一种评估化学物质的单化学方法独立作为风险因素。现有研究中使用的传统统计方法显着在许多环境化学暴露中观察到的典型相关性的挑战，因为以及其他环境和社会经济变量。需要开发和评估对环境癌风险进行建模的统计方法，该方法考虑了大量不同的化学物质对不同的化学类别的影响不同。这项研究的具体目的是1）开发更多全面接触风险模型，并将其应用于儿童白血病的病例对照研究加利福尼亚州含有大量不同化学物质的浓度，2）估计时，与将化学浓度归因于检测极限相关的不确定性化学混合物效应，3）考虑社区社会经济状况和残留混淆估计化学暴露效应时。儿童白血病的研究将受益于环境化学风险分析是因为它是一种癌症，具有不清楚的病因和确定的风险因素仅占美国年度总案件的一小部分。预期的结果研究将是1）新的统计方法来模拟环境癌风险，以考虑环境更全面地接触，同时还考虑与丢失数据有关的不确定性，2）评估来自许多化学类别的化学物质的影响，并鉴定儿童白血病的重要化学物质。这项研究的意义是两倍。首先，考虑多种多样性的新统计方法的新统计方法的开发和评估在考虑不确定性的同时，环境暴露将促进环境流行病学领域研究。其次，这将是童年病例对照研究的首次环境风险分析使用大量相关化学物质估算不同化学类别影响的白血病曝光，同时还调整家庭和社区水平的已知人口危险因素并考虑与丢失数据有关的不确定性。这项工作中开发的方法论方法将适用于许多与多种环境暴露类型的环境暴露相关的其他癌症。