Haplotypes of DNA repair and cell cycle control genes, X-ray exposure, and risk of childhood acute lymphoblastic leukemia
Copyright policy )Haplotypes of DNA repair and cell cycle control genes, X-ray exposure, and risk of childhood acute lymphoblastic leukemia
Acute leukemias of childhood are a heterogeneous group of malignancies characterized by cytogenetic abnormalities, such as translocations and changes in ploidy. These abnormalities may be influenced by altered DNA repair and cell cycle control processes.We examined the association between childhood acute lymphoblastic leukemia (ALL) and 32 genes in DNA repair and cell cycle pathways using a haplotype-based approach, among 377 childhood ALL cases and 448 controls enrolled during 1995-2002.We found that haplotypes in APEX1, BRCA2, ERCC2, and RAD51 were significantly associated with total ALL, while haplotypes in NBN and XRCC4, and CDKN2A were associated with structural and numerical change subtypes, respectively. In addition, we observed statistically significant interaction between exposure to 3 or more diagnostic X-rays and haplotypes of XRCC4 on risk of structural abnormality-positive childhood ALL.These results support a role of altered DNA repair and cell cycle processes in the risk of childhood ALL, and show that this genetic susceptibility can differ by cytogenetic subtype and may be modified by exposure to ionizing radiation. To our knowledge, our study is the first to broadly examine the DNA repair and cell cycle pathways using a haplotype approach in conjunction with X-ray exposures in childhood ALL risk. If confirmed, future studies are needed to identify specific functional SNPs in the regions of interest identified in this analysis.
- National Health Research Institutes Taiwan
- University of California, San Francisco United States
- Vanderbilt University Medical Center United States
- UNIVERSITY OF CALIFORNIA BERKELEY
- Vanderbilt University United States
Male, Cancer Research, 1117 Public Health and Health Services (for), DNA Repair, Epidemiology, cdc (mesh), Preschool (mesh), Risk Factors, 2.1 Biological and endogenous factors, Childhood Leukemia (rcdc), cdc, 32 Biomedical and Clinical Sciences (for-2020), Child, Male (mesh), Genetic Predisposition to Disease (mesh), In Situ Hybridization, In Situ Hybridization, Fluorescence, Cancer, Pediatric, Cancer (rcdc), Humans (mesh), Leukemia, Precursor Cell Lymphoblastic Leukemia-Lymphoma (mesh), Hematology, Single Nucleotide, 1112 Oncology and Carcinogenesis (for), Precursor Cell Lymphoblastic Leukemia-Lymphoma, Pediatric Cancer (rcdc), Oncology, Child, Preschool, Public Health and Health Services, Childhood cancer, X-Rays (mesh), Haplotypes (mesh), Single Nucleotide (mesh), Genotype, Childhood Leukemia, Pediatric Cancer, Oncology and Carcinogenesis, 610, DNA repair, Polymorphism, Single Nucleotide, Fluorescence, Case-Control Studies (mesh), Epidemiology (science-metrix), Rare Diseases (rcdc), Rare Diseases, Risk Factors (mesh), Genetics, Genetic susceptibility, 3211 Oncology and carcinogenesis (for-2020), Humans, Genetic Predisposition to Disease, DNA Repair (mesh), Polymorphism, Preschool, Pediatric (rcdc), Hematology (rcdc), Original Paper, Biomedical and Clinical Sciences, Genetics (rcdc), Genotype (mesh), Fluorescence (mesh), X-Rays, 2.1 Biological and endogenous factors (hrcs-rac), Cancer (hrcs-hc), Genes, cdc, 3211 Oncology and Carcinogenesis (for-2020), Genes, Haplotypes, Case-Control Studies, 4202 Epidemiology (for-2020)
Male, Cancer Research, 1117 Public Health and Health Services (for), DNA Repair, Epidemiology, cdc (mesh), Preschool (mesh), Risk Factors, 2.1 Biological and endogenous factors, Childhood Leukemia (rcdc), cdc, 32 Biomedical and Clinical Sciences (for-2020), Child, Male (mesh), Genetic Predisposition to Disease (mesh), In Situ Hybridization, In Situ Hybridization, Fluorescence, Cancer, Pediatric, Cancer (rcdc), Humans (mesh), Leukemia, Precursor Cell Lymphoblastic Leukemia-Lymphoma (mesh), Hematology, Single Nucleotide, 1112 Oncology and Carcinogenesis (for), Precursor Cell Lymphoblastic Leukemia-Lymphoma, Pediatric Cancer (rcdc), Oncology, Child, Preschool, Public Health and Health Services, Childhood cancer, X-Rays (mesh), Haplotypes (mesh), Single Nucleotide (mesh), Genotype, Childhood Leukemia, Pediatric Cancer, Oncology and Carcinogenesis, 610, DNA repair, Polymorphism, Single Nucleotide, Fluorescence, Case-Control Studies (mesh), Epidemiology (science-metrix), Rare Diseases (rcdc), Rare Diseases, Risk Factors (mesh), Genetics, Genetic susceptibility, 3211 Oncology and carcinogenesis (for-2020), Humans, Genetic Predisposition to Disease, DNA Repair (mesh), Polymorphism, Preschool, Pediatric (rcdc), Hematology (rcdc), Original Paper, Biomedical and Clinical Sciences, Genetics (rcdc), Genotype (mesh), Fluorescence (mesh), X-Rays, 2.1 Biological and endogenous factors (hrcs-rac), Cancer (hrcs-hc), Genes, cdc, 3211 Oncology and Carcinogenesis (for-2020), Genes, Haplotypes, Case-Control Studies, 4202 Epidemiology (for-2020)
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