Department of Pharmacology and Toxicology, University of Navarra, C/Irunlarrea 1, 31009 Pamplona, Spain; IdiSNA, Navarra Institute for Health Research, Spain.
H&TRC - Health & Technology Research Center, ESTeSL - Escola Superior de Tecnologia da Saúde, Instituto Politécnico de Lisboa, Av. D. João II, lote 4.69.01, Parque das Nações, 1990-096 Lisboa, Portugal; Centro de Investigação e Estudos em Saúde Pública, Escola Nacional de Saúde Pública, ENSP, Universidade Nova de Lisboa, Portugal.
Mutat Res Rev Mutat Res. 2020 Jan-Mar;783:108288. doi: 10.1016/j.mrrev.2019.108288. Epub 2019 Nov 9.
The comet assay is a well-accepted biomonitoring tool to examine the effect of dietary, lifestyle, environmental and occupational exposure on levels of DNA damage in human cells. With such a wide range of determinants for DNA damage levels, it becomes challenging to deal with confounding and certain factors are inter-related (e.g. poor nutritional intake may correlate with smoking status). This review describes the effect of intrinsic (i.e. sex, age, tobacco smoking, occupational exposure and obesity) and extrinsic (season, environmental exposures, diet, physical activity and alcohol consumption) factors on the level of DNA damage measured by the standard or enzyme-modified comet assay. Although each factor influences at least one comet assay endpoint, the collective evidence does not indicate single factors have a large impact. Thus, controlling for confounding may be necessary in a biomonitoring study, but none of the factors is strong enough to be regarded a priori as a confounder. Controlling for confounding in the comet assay requires a case-by-case approach. Inter-laboratory variation in levels of DNA damage and to some extent also reproducibility in biomonitoring studies are issues that have haunted the users of the comet assay for years. Procedures to collect specimens, and their storage, are not standardized. Likewise, statistical issues related to both sample-size calculation (before sampling of specimens) and statistical analysis of the results vary between studies. This review gives guidance to statistical analysis of the typically complex exposure, co-variate, and effect relationships in human biomonitoring studies.
彗星试验是一种广泛接受的生物监测工具，用于检测饮食、生活方式、环境和职业暴露对人体细胞 DNA 损伤水平的影响。由于 DNA 损伤水平的决定因素如此广泛，处理混杂因素变得具有挑战性，并且某些因素是相互关联的（例如，营养摄入不良可能与吸烟状况相关）。本综述描述了内在（即性别、年龄、吸烟、职业暴露和肥胖）和外在（季节、环境暴露、饮食、体力活动和饮酒）因素对标准或酶修饰彗星试验测量的 DNA 损伤水平的影响。尽管每个因素至少影响一个彗星试验终点，但综合证据表明没有单一因素有很大影响。因此，在生物监测研究中可能需要控制混杂因素，但没有一个因素强大到足以被视为先验混杂因素。在彗星试验中控制混杂因素需要逐个案例的方法。多年来，DNA 损伤水平的实验室间变异性以及在一定程度上生物监测研究的可重复性一直困扰着彗星试验的使用者。样本采集和储存的程序尚未标准化。同样，与样本大小计算（在采样之前）和结果的统计分析相关的统计问题在研究之间也有所不同。本综述为人类生物监测研究中典型复杂的暴露、协变量和效应关系的统计分析提供了指导。
