Challenges identifying genetic determinants of pediatric cancers--the childhood leukemia experience

Familial Cancer
D SinnettM Krajinovic

Abstract

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 variation plays 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 case-control 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 m...Continue Reading

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