Norppa H, Bonassi S, Hansteen I-L, Hagmar L, Strömberg U, Rössner P, Boffetta P, Lindholm C, Gundy S, Lazutka J, Cebulska-Wasilewska A, Fabiánová E, Srám R J, Knudsen L E, Barale R, Fucic A
New Technologies and Risks, Finnish Institute of Occupational Health, FI-00250 Helsinki, Finland.
Mutat Res. 2006 Aug 30;600(1-2):37-45. doi: 10.1016/j.mrfmmm.2006.05.030. Epub 2006 Jul 11.
Previous studies have suggested that the frequency of chromosomal aberrations (CAs), but not of sister chromatid exchanges (SCEs), predicts cancer risk. We have further examined this relationship in European cohorts comprising altogether almost 22,000 subjects, in the framework of a European collaborative project (CancerRiskBiomarkers). The present paper gives an overview of some of the results of the project, especially as regards CAs and SCEs. The results confirm that a high level of CAs is associated with an increased risk of cancer and indicate that this association does not depend on the time between CA analysis and cancer detection, i.e., is obviously not explained by undetected cancer. The present evidence indicates that both chromatid-type and chromosome-type CAs predict cancer, even though some data suggest that chromosome-type CAs may have a more pronounced predictive value than chromatid-type CAs. CA frequency appears to predict cancers at various sites, although there seems to be a particular association with gastrointestinal cancers. SCE frequency does not appear to have cancer predictive value, at least partly due to uncontrollable technical variation. A number of genetic polymorphisms of xenobiotic metabolism, DNA repair, and folate metabolism affect the level of CAs and might collectively contribute to the cancer predictivity of CAs. Other factors that may influence the association between CAs and cancer include, e.g., exposure to genotoxic carcinogens and internal generation of genotoxic species. Although the association between CA level and cancer is seen at the group level, an association probably also exists for the individual, although it is not known if an individual approach could be feasible. However, group level evidence should be enough to support the use of CA analysis as a tool in screening programs and prevention policies in occupational and environmental health.
以往研究表明,染色体畸变(CA)的频率而非姐妹染色单体交换(SCE)的频率可预测癌症风险。在一项欧洲合作项目(CancerRiskBiomarkers)的框架下,我们在总共近22,000名受试者的欧洲队列中进一步研究了这种关系。本文概述了该项目的一些结果,特别是关于CA和SCE的结果。结果证实,高水平的CA与癌症风险增加相关,并表明这种关联不取决于CA分析与癌症检测之间的时间,即显然不是由未检测到的癌症所解释。目前的证据表明,染色单体型和染色体型CA均能预测癌症,尽管一些数据表明染色体型CA可能比染色单体型CA具有更显著的预测价值。CA频率似乎能预测各个部位的癌症,尽管似乎与胃肠道癌症存在特别的关联。SCE频率似乎没有癌症预测价值,至少部分原因是技术变异无法控制。一些外源性物质代谢、DNA修复和叶酸代谢的基因多态性会影响CA的水平,并可能共同促成CA的癌症预测性。其他可能影响CA与癌症之间关联的因素包括,例如,接触基因毒性致癌物和基因毒性物质的内源性产生。尽管在群体水平上可以看到CA水平与癌症之间的关联,但个体之间可能也存在关联,尽管尚不清楚个体方法是否可行。然而,群体水平的证据应该足以支持将CA分析用作职业和环境卫生筛查项目及预防政策中的一种工具。