Sinnett Daniel, N'Diaye Nina, Labuda Damian, Krajinovic Maja
Service d'hématologie-oncologie, Centre de cancérologie Charles-Bruneau, Hôpital Sainte-Justine, Département de pédiatrie, Université de Montréal, 3175 Côte Sainte-Catherine, Montréal, Québec, H3T 1C5 Canada.
Bull Cancer. 2006 Sep;93(9):857-65.
Pediatric cancers affect approximately 1 in every 500 children before the age of 15. Little is known about the etiology of this heterogeneous group of diseases despite the fact they constitute the major cause of death by disease among this population. Because of its relatively high prevalence, most of the work done in pediatric oncogenetics has been focused on leukemias, particularly acute lymphoblastic leukemia (ALL). Although it is now well accepted that genetic variations play a significant role in determining individual's cancer susceptibility, few studies have explored genetic susceptibility to childhood leukemia with respect to common polymorphisms. The biochemical and genetic mechanisms contributing to cancer susceptibility are numerous and can be grouped into broad categories: 1) cellular growth and differentiation, 2) DNA replication and repair, 3) metabolism of carcinogens, 4) apoptosis, 5) oxidative stress response and 6) cell cycle. To evaluate whether candidate genes in these pathways are involved in childhood leukemogenesis, we conducted association studies. We showed that leukemogenesis in children may be associated with DNA variants in some of these genes and that the combination of genotypes seems to be more predictive of risk then either of them independently. We also observed that, at least at some loci, the parental genetics might be important in predicting the risk of cancer in this pediatric model of a complex disease. Taken together, these results indicate that the investigation of a single enzyme and/or a single genotype might not be sufficient to explain the etiology of childhood leukemia because of the complexity of the environment and that of the inter-individual variability in cancer susceptibility.
15岁前，每500名儿童中约有1人受小儿癌症影响。尽管这类异质性疾病是该人群中因病死亡的主要原因，但人们对其病因知之甚少。由于其发病率相对较高，小儿肿瘤遗传学领域的大部分研究都集中在白血病上，尤其是急性淋巴细胞白血病（ALL）。虽然现在人们普遍认为基因变异在决定个体患癌易感性方面起着重要作用，但很少有研究探讨常见多态性与儿童白血病遗传易感性之间的关系。导致癌症易感性的生化和遗传机制众多，可大致分为以下几类：1）细胞生长与分化；2）DNA复制与修复；3）致癌物代谢；4）细胞凋亡；5）氧化应激反应；6）细胞周期。为了评估这些途径中的候选基因是否参与儿童白血病的发生，我们进行了关联研究。我们发现儿童白血病的发生可能与其中一些基因的DNA变异有关，而且基因型的组合似乎比单个基因型更能预测风险。我们还观察到，至少在某些基因座上，在这个复杂疾病的小儿模型中，父母的基因可能对预测癌症风险很重要。综上所述，这些结果表明，由于环境的复杂性以及个体间癌症易感性的差异，仅研究单一酶和/或单一基因型可能不足以解释儿童白血病的病因。
