Rothman N, Wacholder S, Caporaso N E, Garcia-Closas M, Buetow K, Fraumeni J F
Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, MD 20892, USA.
Biochim Biophys Acta. 2001;1471(2):C1-10. doi: 10.1016/s0304-419x(00)00021-4.
Overwhelming evidence indicates that environmental exposures, broadly defined, are responsible for most cancer. There is reason to believe, however, that relatively common polymorphisms in a wide spectrum of genes may modify the effect of these exposures. We discuss the rationale for using common polymorphisms to enhance our understanding of how environmental exposures cause cancer and comment on epidemiologic strategies to assess these effects, including study design, genetic and statistical analysis, and sample size requirements. Special attention is given to sources of potential bias in population studies of gene--environment interactions, including exposure and genotype misclassification and population stratification (i.e., confounding by ethnicity). Nevertheless, by merging epidemiologic and molecular approaches in the twenty-first century, there will be enormous opportunities for unraveling the environmental determinants of cancer. In particular, studies of genetically susceptible subgroups may enable the detection of low levels of risk due to certain common exposures that have eluded traditional epidemiologic methods. Further, by identifying susceptibility genes and their pathways of action, it may be possible to identify previously unsuspected carcinogens. Finally, by gaining a more comprehensive understanding of environmental and genetic risk factors, there should emerge new clinical and public health strategies aimed at preventing and controlling cancer.
大量证据表明，广义上的环境暴露是大多数癌症的病因。然而，有理由相信，广泛基因中的相对常见的多态性可能会改变这些暴露的影响。我们讨论了利用常见多态性来增进我们对环境暴露如何导致癌症的理解的基本原理，并对评估这些影响的流行病学策略进行了评论，包括研究设计、基因和统计分析以及样本量要求。特别关注基因 - 环境相互作用的人群研究中潜在偏差的来源，包括暴露和基因型错误分类以及人群分层（即种族混杂）。尽管如此，通过在21世纪融合流行病学和分子方法，将有巨大机会揭示癌症的环境决定因素。特别是，对遗传易感亚组的研究可能能够检测出某些常见暴露导致的低水平风险，而这些风险是传统流行病学方法所遗漏的。此外，通过识别易感基因及其作用途径，有可能识别出以前未被怀疑的致癌物。最后，通过更全面地了解环境和遗传风险因素，应该会出现旨在预防和控制癌症的新的临床和公共卫生策略。
