Genetic Variation in H2AFX Contributes to Risk of Non–Hodgkin Lymphoma
| Autor: | Payal Sipahimalani, John J. Spinelli, Randy D. Gascoyne, Karey Shumansky, Agnes S. Lai, Karen L. Novik, Amy C. MacArthur, Joseph M. Connors, Angela Brooks-Wilson, Stephen Leach, Richard P. Gallagher |
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| Rok vydání: | 2007 |
| Předmět: |
Adult
Male Candidate gene Genotype Epidemiology Molecular Sequence Data Follicular lymphoma Single-nucleotide polymorphism Biology Polymerase Chain Reaction Polymorphism Single Nucleotide Linkage Disequilibrium Histones Risk Factors immune system diseases Sequence Homology Nucleic Acid hemic and lymphatic diseases Genetic variation medicine Genetic predisposition Animals Humans Genetic Predisposition to Disease Aged Genetic association Genetics Base Sequence Lymphoma Non-Hodgkin Middle Aged medicine.disease Biological Evolution Oncology Case-Control Studies Female Mantle cell lymphoma |
| Zdroj: | Cancer Epidemiology, Biomarkers & Prevention. 16:1098-1106 |
| ISSN: | 1538-7755 1055-9965 |
| DOI: | 10.1158/1055-9965.epi-06-0639 |
| Popis: | Non–Hodgkin lymphoma (NHL) comprises a group of lymphoid tumors that have in common somatic translocations. H2AFX encodes a key histone involved in the detection of the DNA double-stranded breaks that can lead to translocations. H2afx is a dosage-dependent gene that protects against B-cell lymphomas in mice, making its human orthologue an ideal candidate gene for susceptibility to lymphoma. We did a population-based genetic association study of H2AFX variants in 487 NHL cases and 531 controls. Complete resequencing of the human H2AFX gene in 95 NHL cases was done to establish the spectrum of variation in affected individuals; this was followed by both direct and indirect tests for association at the level of individual single nucleotide polymorphisms (SNP) and as haplotypes. Homozygosity for the AA genotype of a SNP 417 bp upstream of the translational start of H2AFX is strongly associated [odds ratio (OR), 0.54; P = 0.001] with protection from NHL. We find a strong association of this SNP with the follicular lymphoma subtype of NHL (AA genotype: OR, 0.40; P = 0.004) and with mantle cell lymphoma (AA genotype: OR, 0.20; P = 0.01) that remains significant after adjustment for the false discovery rate, but not with diffuse large B-cell lymphoma. These data support the hypothesis that genetic variation in the H2AFX gene influences genetic susceptibility or resistance to some subtypes of NHL by contributing to the maintenance of genome stability. (Cancer Epidemiol Biomarkers Prev 2007;16(6):1098–106) |
| Databáze: | OpenAIRE |
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