Challenges identifying genetic determinants of pediatric cancers--the childhood leukemia experience.
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Issue Date
2006
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Show full item recordAbstract
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 more predictive of risk than 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.Citation
Fam. Cancer 2006, 5 (1):35-47Journal
Familial cancerPubMed ID
16528607Additional Links
http://www.springerlink.com/content/82t5846pw287r4q3/Type
ArticleLanguage
enDescription
KEYWORDS CLASSIFICATION: biomarkers of exposure & effect: field studies;Canada;cancer epidemiology;Child;Child,Preschool;Confidence Intervals;Cytochrome P-450 Enzyme System;enzymology;epidemiology;etiology;Female;genetics;Gene Expression Regulation,Neoplastic;Genetic Predisposition to Disease;Genotype;Glutathione;Glutathione Transferase;Humans;Incidence;Leukemia,Lymphocytic,Acute;metabolism;Male;Odds Ratio;Oxidative Stress;physiology;Pediatrics;Pedigree;Polymorphism,Genetic;Prognosis;Research;Risk Assessment;field studies.ISSN
1389-9600ae974a485f413a2113503eed53cd6c53
10.1007/s10689-005-2574-4
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