An XRCC1 polymorphism is associated with the outcome of patients with lymphoma undergoing autologous stem cell transplant

Abstract

High-dose chemotherapy supported by autologous stem cell transplant (ASCT) remains the treatment of choice for patients with lymphoma failing first-line chemotherapy. Recent evidence suggests a relationship between the genetic variations in genes involved in DNA repair and the outcome of patients with a number of malignancies. In this work, we retrospectively evaluated the influence of an XRCC1 polymorphism (rs25487) on the treatment results in a series of 73 patients with lymphoma subjected to ASCT. The factors correlated to overall survival were the disease status at transplant and XRCC1 genotype. Carriers of a mutant A allele had a two-fold higher risk of death than those with the wild-type genotype. In addition, patients harboring one or two copies of the A allele (GA/AA) were 4.5-fold more likely to develop therapy-related acute myeloid (t-AML). Thus, the cumulative probability of t-AML at 10 years was 37 ± 13% in patients with the mutant A allele as compared to 8.5 ± 6% in the remaining cases (p = 0.04). Our findings suggest that genetic variation in the DNA repair gene XRCC1 may play a role in the results of transplant in patients with lymphoma.

Keywords:

• Lymphoma
• genetic polymorphisms
• DNA repair
• XRCC1 gene
• transplant

Acknowledgements

This study was financially supported by grant AP027/07 from the Conselleria de Sanitat, Generalitat Valenciana, and by an unrestricted grant from Celgene Corporation.

Potential conflict of interest:

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