International Prevention Research Institute, 95 cours Lafayette, 69006 Lyon, France.
Carcinogenesis. 2010 Jan;31(1):121-6. doi: 10.1093/carcin/bgp269. Epub 2009 Dec 3.
There are different reasons for the increase in the use of biomarkers in cancer epidemiology which is as follows: (i) the fact that the identification of new carcinogens, characterized by complex exposure circumstances and weak effects, has become increasingly difficult with traditional epidemiological approaches; (ii) the increasing understanding of mechanisms of carcinogenesis and (iii) technical developments in molecular biology and genetics. While a distinction is made between biomarkers of exposure, intermediate events, disease, outcome and susceptibility, their integration in a unique conceptual model is needed. The use of exposure biomarkers in cancer epidemiology aims at measuring the biologically relevant exposure more validly and precisely. In some instances, there is an obvious improvement in using an exposure biomarker, as in the case of urinary markers of aflatoxin and tobacco-specific nitrosamines. Intermediate (effect) biomarkers measure early--in general non-persistent--biological events that take place in the continuum between exposure and cancer development. These include cellular or tissue toxicity, chromosomal alterations, changes in DNA, RNA and protein expression and alterations in functions relevant to carcinogenesis (e.g. DNA repair, immunological response, etc.). The analysis of acquired TP53 mutations is an example of the potentially important. Biomarkers should be validated and consideration of sources of bias and confounding in molecular epidemiology studies should be no less stringent than in other types of epidemiological studies. The overarching goal is the integration of different types of biomarkers to derive risk and outcome profiles for healthy individuals as well as patients.
（i）传统流行病学方法识别新的致癌物变得越来越困难，这些致癌物具有复杂的暴露环境和微弱的作用；（ii）对致癌机制的认识不断加深；（iii）分子生物学和遗传学的技术发展。虽然区分了暴露标志物、中间事件、疾病、结局和易感性标志物，但需要将它们整合到一个独特的概念模型中。癌症流行病学中使用暴露标志物的目的是更有效地和更精确地测量具有生物学相关性的暴露。在某些情况下，使用暴露标志物的效果明显改善，例如尿液中黄曲霉毒素和烟草特异性亚硝胺的标志物。中间（效应）标志物测量发生在暴露和癌症发展之间连续体中的早期——通常是非持久性的——生物学事件。这些事件包括细胞或组织毒性、染色体改变、DNA、RNA 和蛋白质表达的变化以及与致癌作用相关的功能改变（例如 DNA 修复、免疫反应等）。分析获得的 TP53 突变就是一个潜在重要的例子。生物标志物应经过验证，在分子流行病学研究中考虑偏倚和混杂因素的来源不应比其他类型的流行病学研究更为宽松。总体目标是整合不同类型的生物标志物，为健康个体以及患者得出风险和结局概况。
