Division of the National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, USA.
Division of Environmental Health Sciences, University of California Berkeley, School of Public Health, Berkeley, California, USA.
Environ Health Perspect. 2021 Mar;129(3):35003. doi: 10.1289/EHP8525. Epub 2021 Mar 30.
People are exposed to numerous chemicals throughout their lifetimes. Many of these chemicals display one or more of the key characteristics of carcinogens or interact with processes described in the hallmarks of cancer. Therefore, evaluating the effects of chemical mixtures on cancer development is an important pursuit. Challenges involved in designing research studies to evaluate the joint action of chemicals on cancer risk include the time taken to perform the experiments because of the long latency and choosing an appropriate experimental design.
The objectives of this work are to present the case for developing a research program on mixtures of environmental chemicals and cancer risk and describe recommended approaches.
A working group comprising the coauthors focused attention on the design of mixtures studies to inform cancer risk assessment as part of a larger effort to refine the key characteristics of carcinogens and explore their application. Working group members reviewed the key characteristics of carcinogens, hallmarks of cancer, and mixtures research for other disease end points. The group discussed options for developing tractable projects to evaluate the joint effects of environmental chemicals on cancer development.
Three approaches for developing a research program to evaluate the effects of mixtures on cancer development were proposed: a chemical screening approach, a transgenic model-based approach, and a disease-centered approach. Advantages and disadvantages of each are discussed. https://doi.org/10.1289/EHP8525.
人们在一生中会接触到众多化学物质。这些化学物质中的许多物质表现出一种或多种致癌物的关键特征，或与癌症特征中描述的过程相互作用。因此，评估化学混合物对癌症发展的影响是一项重要的研究课题。在设计研究以评估化学物质对癌症风险的联合作用时，面临的挑战包括由于潜伏期长而需要花费大量时间来进行实验，以及选择合适的实验设计。
本研究旨在提出制定环境化学物质与癌症风险混合物研究计划的理由，并描述推荐方法。
一个由共同作者组成的工作组，重点关注混合物研究的设计，以告知癌症风险评估，这是对致癌物关键特征进行细化并探索其应用的更大努力的一部分。工作组的成员回顾了致癌物的关键特征、癌症的标志性特征以及其他疾病终点的混合物研究。该小组讨论了制定可行项目以评估环境化学物质对癌症发展的联合影响的方案。
提出了三种用于制定评估混合物对癌症发展影响的研究计划的方法：化学筛选方法、基于转基因模型的方法和以疾病为中心的方法。讨论了每种方法的优缺点。https://doi.org/10.1289/EHP8525.
