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The genotype distribution of the XRCC1 gene indicates a role for base excision repair in the development of therapy-related acute myeloblastic leukemia

Seedhouse, Claire; Bainton, Rowena; Lewis, Michael; Harding, Alexander; Russell, Nigel; Das-Gupta, Emma

Authors

Rowena Bainton

Michael Lewis

Alexander Harding

Nigel Russell

Emma Das-Gupta



Abstract

Polymorphisms in several DNA repair genes have been described. These polymorphisms may affect DNA repair capacity and modulate cancer susceptibility by means of gene-environment interactions. We investigated DNA repair capacity and its association with acute myeloblastic leukemia (AML). We studied polymorphisms in 3 DNA repair genes: XRCC1, XRCC3, and XPD. We also assessed the incidence of a functional polymorphism in theNQO1 gene, which is involved in protection of cells from oxidative damage. We genotyped the polymorphisms by using polymerase chain reaction–restriction fragment-length polymorphism analysis in 134 patients with de novo AML, 34 with therapy-related AML (t-AML), and 178 controls. The distributions of theXRCC3 Thr241Met and NQO1 Pro187Ser genotypes were not significantly different in patients and controls. However, the distribution of the XRCC1 Arg399Gln genotypes was significantly different when comparing the t-AML and control groups (χ2, P = .03). The presence of at least oneXRCC1 399Gln allele indicated a protective effect for the allele in controls compared with patients with t-AML (odds ratio 0.44; 95% confidence interval, 0.20-0.93). We found no interactions between the XRCC1 or XRCC3 and NQO1genotypes. We also found no differences in the distribution of the XPD Lys751Gln or XRCC1 Arg194Trp genotypes. Our data provide evidence of a protective effect against AML in individuals with at least one copy of the variant XRCC1 399Gln allele compared with those homozygous for the common allele.

Citation

Seedhouse, C., Bainton, R., Lewis, M., Harding, A., Russell, N., & Das-Gupta, E. (2002). The genotype distribution of the XRCC1 gene indicates a role for base excision repair in the development of therapy-related acute myeloblastic leukemia. Blood, 100(10), 3761-3766. https://doi.org/10.1182/blood-2002-04-1152

Journal Article Type Article
Acceptance Date Jul 1, 2002
Online Publication Date Nov 15, 2002
Publication Date 2002
Deposit Date Apr 5, 2024
Journal Blood
Print ISSN 0006-4971
Electronic ISSN 1528-0020
Publisher American Society of Hematology
Peer Reviewed Peer Reviewed
Volume 100
Issue 10
Pages 3761-3766
DOI https://doi.org/10.1182/blood-2002-04-1152
Public URL https://nottingham-repository.worktribe.com/output/32755148
Publisher URL https://ashpublications.org/blood/article/100/10/3761/106275/The-genotype-distribution-of-the-XRCC1gene