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- W2010032004 abstract "Graft versus host disease (GVHD) remains a major source of morbidity and mortality among patients undergoing hematopoietic cell transplants (HCT). Tissue damage as a result of treatment is the initiating event in the pathogenesis of GVHD and variations in DNA repair can influence the amount of tissue damage in response to treatment modalities used in HCT. Since DNA damage caused by therapeutic agents such as alkylating agents and ionizing radiation used frequently in pre- HCT conditioning regimens is commonly repaired by the base excision repair (BER) pathway we hypothesized that genetic polymorphisms in the BER pathway will be associated with GVHD after HCT. We evaluated the association between single nucleotide polymorphisms (SNPs) (n= 179) in the BER pathway with acute GVHD and chronic GVHD in a cohort of 470 recipients who underwent allogeneic HCT for treatment of hematologic malignancies at the University of Minnesota. After adjustment for donor type, diagnosis, disease status at transplant and gender mismatch, two SNPs in RFC1 (Replication Factor C) gene (rs1057807 and rs4975003) were associated with a decreased risk of grade II-IV acute GVHD (HR:0.74-0.77; p≤0.01) and one SNP, rs6844176, in RFC1 gene was associated with increased risk of grade II-IV acute GVHD (HR:1.39, p=0.001). The rs3730914 SNP in the LIG1 (Ligase I) gene was also associated with a decreased risk of grade III-IV acute GVHD (HR: 0.38; p=0.005). One SNP, rs1805410, in the PARP1 (poly ADP-ribose polymerase 1) gene was associated with increased risk of chronic GVHD (HR: 1.44; p=0.01) post HCT. These findings suggest that SNPs in the BER pathway can be used as genetic biomarkers to predict individuals at high risk for GVHD. If these findings are confirmed, modulation of pre-transplant conditioning may alter risk in these patients. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4656." @default.
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- W2010032004 date "2010-04-15" @default.
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- W2010032004 title "Abstract 4656: DNA repair polymorphisms as predictors of Graft-versus-Host Disease after allogeneic hematopoietic cell transplants" @default.
- W2010032004 doi "https://doi.org/10.1158/1538-7445.am10-4656" @default.
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