Anderson Lucy M
Laboratory of Comparative Carcinogenesis, National Cancer Institute at Frederick, Frederick, MD 21702, USA.
Mutat Res. 2006 Sep 28;608(2):136-56. doi: 10.1016/j.mrgentox.2006.02.016. Epub 2006 Jul 10.
Cancer in children is a major concern in many countries. An important question is whether these childhood cancers are caused by something, or are just tragic random events. Causation of at least some children's cancers is suggested by direct and indirect evidence, including epidemiological data, and animal studies that predict early life sensitivity of humans to carcinogenic effects. Candidate risk factors include genotoxic agents (chemicals and radiation), but also diet/nutrition, and infectious agents/immune responses. With regard to likelihood of risks posed by genotoxicants, there are pros and cons. The biological properties of fetuses and infants are consistent with sensitivity to preneoplastic genotoxic damage. Recent studies of genetic polymorphisms in carcinogen-metabolizing enzymes confirm a role for chemicals. On the other hand, in numerous epidemiological studies, associations between childhood cancers and exposure to genotoxicants, including tobacco smoke, have been weak and hard to reproduce. Possibly, sensitive genetic or ontogenetic subpopulations, and/or co-exposure situations need to be discovered to allow identification of susceptible individuals and their risk factors. Among the critical knowledge gaps needing to be bridged to aid in this effort include detailed tissue and cellular ontogeny of carcinogen metabolism and DNA repair enzymes, and associations of polymorphisms in DNA repair enzymes with childhood cancers. Perinatal bioassays in animals of specific environmental candidates, for example, benzene, could help guide epidemiology. Genetically engineered animal models could be useful for identification of chemical effects on specific genes. Investigations of interactions between factors may be key to understanding risk. Finally, fathers and newborn infants should receive more attention as especially sensitive targets.
儿童癌症是许多国家的主要关切问题。一个重要问题是，这些儿童癌症是由某些因素引起的，还是仅仅是悲惨的随机事件。包括流行病学数据以及预测人类早期生命对致癌作用敏感性的动物研究在内的直接和间接证据表明，至少某些儿童癌症存在病因。候选风险因素包括遗传毒性物质（化学物质和辐射），但也包括饮食/营养以及感染因子/免疫反应。关于遗传毒性物质带来风险的可能性，存在利弊。胎儿和婴儿的生物学特性与对肿瘤前遗传毒性损伤的敏感性一致。近期对致癌物代谢酶基因多态性的研究证实了化学物质的作用。另一方面，在众多流行病学研究中，儿童癌症与接触遗传毒性物质（包括烟草烟雾）之间的关联一直很微弱且难以重现。可能需要发现敏感的遗传或个体发育亚群以及/或共同暴露情况，以便识别易感个体及其风险因素。为助力这一工作而需要填补的关键知识空白包括致癌物代谢和DNA修复酶的详细组织和细胞个体发育，以及DNA修复酶基因多态性与儿童癌症的关联。对特定环境候选物（例如苯）进行动物围产期生物测定有助于指导流行病学研究。基因工程动物模型可能有助于识别化学物质对特定基因的影响。研究因素之间的相互作用可能是理解风险的关键。最后，父亲和新生儿作为特别敏感的目标应受到更多关注。
