Clavel Jacqueline
INSERM, UMR-S754, université Paris-Sud, 16, av. Paul-Vaillant-Couturier, 94807 Villejuif, France.
C R Biol. 2007 Apr;330(4):306-17. doi: 10.1016/j.crvi.2007.02.012. Epub 2007 Apr 5.
Cancer epidemiology has undergone marked development since the 1950s. One of the most spectacular and specific contributions was the demonstration of the massive effect of smoking on the occurrence of lung, larynx, and bladder cancer. Major chemical, physical, and biological carcinogenic agents have been identified in the working environment and in the overall environment. The chain of events from environmental exposures to cancer requires hundreds of polymorphic genes coding for proteins involved in the transport and metabolism of xenobiotics, or in repair, or in an immune or inflammatory response. The multifactorial and multistage characteristics of cancer create the theoretical conditions for statistical interactions that have been exceptionally detected. Over the last two decades, a considerable mass of data has been generated, mostly addressing the interactions between smoking and xenobiotic-metabolizing enzymes in smoking-related cancers. They were sometimes considered disappointing, but they actually brought a lot of information and raised many methodological issues. In parallel, the number of polymorphisms that can be considered candidate per function increased so much that multiple testing has become a major issue, and genome wide-screening approaches have more and more gained in interest. Facing the resulting complexity, some instruments are being set up: our studies are now equipped with carefully sampled biological collections, high-throughput genotyping systems are becoming available, work on statistical methodologies is ongoing, bioinformatics databases are growing larger and access to them is becoming simpler; international consortiums are being organized. The roles of environmental and genetic factors are being jointly elucidated. The basic rules of epidemiology, which are demanding with respect to sampling, with respect to the histological and molecular criteria for cancer classification, with respect to the evaluation of environmental exposures, their timeframes, quantification and covariables, with respect to study size and with respect to the rigor of multivariate analyses, are more pertinent than ever before.
自20世纪50年代以来，癌症流行病学有了显著发展。其中最引人注目的具体贡献之一是证明了吸烟对肺癌、喉癌和膀胱癌发生的巨大影响。在工作环境和整体环境中已确定了主要的化学、物理和生物致癌因素。从环境暴露到癌症的一系列事件需要数百个多态性基因，这些基因编码参与外源性物质运输和代谢、修复、免疫或炎症反应的蛋白质。癌症的多因素和多阶段特征为已被异常检测到的统计相互作用创造了理论条件。在过去二十年中，产生了大量数据，主要涉及吸烟与吸烟相关癌症中外源性物质代谢酶之间的相互作用。这些数据有时被认为令人失望，但实际上它们带来了很多信息并引发了许多方法学问题。与此同时，每个功能可被视为候选的多态性数量增加得如此之多，以至于多重检验已成为一个主要问题，全基因组筛选方法越来越受到关注。面对由此产生的复杂性，一些工具正在建立：我们的研究现在配备了精心采样的生物样本库，高通量基因分型系统正在变得可用，统计方法的研究正在进行中，生物信息学数据库越来越大且访问变得更简单；国际联盟正在组建。环境和遗传因素的作用正在共同阐明。流行病学的基本规则，在抽样、癌症分类的组织学和分子标准、环境暴露评估、其时间框架、量化和协变量、研究规模以及多变量分析的严谨性方面要求很高，比以往任何时候都更具相关性。
