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

2.50
Hdl Handle:
http://hdl.handle.net/10146/65058
Title:
Challenges identifying genetic determinants of pediatric cancers--the childhood leukemia experience.
Authors:
Sinnett, Daniel; Labuda, Damian; Krajinovic, Maja
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 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):35-47
Journal:
Familial cancer
Issue Date:
2006
URI:
http://hdl.handle.net/10146/65058
DOI:
10.1007/s10689-005-2574-4
PubMed ID:
16528607
Additional Links:
http://www.springerlink.com/content/82t5846pw287r4q3/
Type:
Article
Language:
en
Description:
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:
1389-9600
Appears in Collections:
Articles with annotation

Full metadata record

DC FieldValue Language
dc.contributor.authorSinnett, Daniel-
dc.contributor.authorLabuda, Damian-
dc.contributor.authorKrajinovic, Maja-
dc.date.accessioned2009-04-16T12:31:03Z-
dc.date.available2009-04-16T12:31:03Z-
dc.date.issued2006-
dc.identifier.citationFam. Cancer 2006, 5 (1):35-47en
dc.identifier.issn1389-9600-
dc.identifier.pmid16528607-
dc.identifier.doi10.1007/s10689-005-2574-4-
dc.identifier.urihttp://hdl.handle.net/10146/65058-
dc.descriptionKEYWORDS 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.en
dc.description.abstractPediatric 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.en
dc.language.isoenen
dc.relation.urlhttp://www.springerlink.com/content/82t5846pw287r4q3/en
dc.subjectCarcinogen metabolismen
dc.subjectComplex diseaseen
dc.subjectFolateen
dc.subjectGene–gene interactionen
dc.subjectLeukemiaen
dc.subjectOncogeneticsen
dc.subjectParental geneticsen
dc.subjectPediatric canceren
dc.subjectPolymorphismsen
dc.subject.meshChild-
dc.subject.meshChild, Preschool-
dc.subject.meshConfidence Intervals-
dc.subject.meshCytochrome P-450 Enzyme System-
dc.subject.meshFemale-
dc.subject.meshGene Expression Regulation, Neoplastic-
dc.subject.meshGenetic Predisposition to Disease-
dc.subject.meshGenotype-
dc.subject.meshGlutathione Transferase-
dc.subject.meshHumans-
dc.subject.meshIncidence-
dc.subject.meshMale-
dc.subject.meshOdds Ratio-
dc.subject.meshOxidative Stress-
dc.subject.meshPediatrics-
dc.subject.meshPedigree-
dc.subject.meshPolymorphism, Genetic-
dc.subject.meshPrecursor Cell Lymphoblastic Leukemia-Lymphoma-
dc.subject.meshPrognosis-
dc.subject.meshRisk Assessment-
dc.titleChallenges identifying genetic determinants of pediatric cancers--the childhood leukemia experience.en
dc.typeArticleen
dc.identifier.journalFamilial canceren

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