Abstract
Abstract 870
Introduction:
Despite recent advances in technology and supportive care, hematopoietic cell transplant (HCT) continues to be associated with high morbidity and mortality. Since the therapies used in HCT induce DNA damage that is repaired by the base excision repair (BER) pathway we hypothesized that single nucleotide polymorphisms (SNPs) in BER genes may influence HCT outcomes.
Methods:
We evaluated the association between tagSNPs and functionally important SNPs (n= 179) in the BER pathway with transplant related mortality at one year (TRM) and disease relapse in a cohort of 470 recipients of allogeneic HCT for hematologic malignancies at the University of Minnesota between 1998 and 2007 from a HLA-identical sibling donor, HLA-matched or mismatched unrelated donor (URD) or single umbilical cord graft.
Results:
After adjustment for age at transplant, donor type, race, and conditioning regimen, four SNPs in OGGI, LIG3 and MUTYH1 genes (rs159153, rs3135974, rs3219463, rs3219476) were associated with increased risk of TRM whereas two SNPs in TDG gene (rs167715, rs2374327) were associated with decreased risk of TRM at one year (p≤0.01). Patients with increasing numbers of deleterious alleles in the BER pathway showed an increased cumulative incidence of TRM at one year (14% for ≤ 1 deleterious allele vs. 51% for ≥ 4 deleterious alleles; p<0.001). One SNP, rs3135974, in LIG3 gene was associated with decreased risk of disease relapse (p<0.001) post HCT.
Conclusions:
Single nucleotide polymorphisms in the BER pathway are significantly associated with both TRM and disease relapse, thus supporting the hypothesis that genetic polymorphisms in the BER pathway are involved in the pathophysiology of TRM and disease relapse. If confirmed in independent cohorts, these SNPs may indicate patients who might benefit from altered or less DNA damaging conditioning regimens.
Disclosures:
No relevant conflicts of interest to declare.
Single Nucleotide Polymorphisms of DNA Base-excision Repair Genes (APE1, OGG1 and XRCC1) Associated with Breast Cancer Risk in a Chinese Population
