Progress in the epidemiological understanding of gene-environment interactions in major diseases: cancer
Progress in the epidemiological understanding of gene-environment interactions in major diseases: cancer
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DOI：
10.1016/j.crvi.2007.02.012
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发表时间：
2007-04-01
影响因子：
2
通讯作者：
Clavel, Jacqueline
中科院分区：
文献类型：
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作者：
Clavel, Jacqueline
自20世纪50年代以来，癌症流行病学有了长足的发展。最引人注目和最具体的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。已在工作环境和整个环境中确定了主要的化学、物理和生物致癌物质。从环境暴露到癌症的一连串事件需要数百个多态基因编码参与外源物质的运输和新陈代谢、修复或免疫或炎症反应的蛋白质。癌症的多因素和多阶段特征为统计相互作用创造了理论条件，这些统计相互作用已经被异常检测到。在过去的二十年里，已经产生了大量的数据，主要是关于吸烟和吸烟相关癌症中的外源代谢酶之间的相互作用。它们有时被认为令人失望，但它们实际上带来了大量信息，并提出了许多方法问题。与此同时，可以被认为是每个功能的候选基因的多态数量如此之多，以至于多重测试已经成为一个主要问题，基因组广泛筛选方法已经越来越引起人们的兴趣。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仔细采样的生物样本，高通量基因分型系统正在变得可用，统计方法的工作正在进行，生物信息学数据库越来越大，获取它们变得越来越简单；国际财团正在组织。环境因素和遗传因素的作用正在联合阐明。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、环境暴露的评估、时间范围、量化和协变量、研究规模和多变量分析的严谨性方面比以往任何时候都更加切合实际。
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.