title: 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.
authors.affiliation: Servicio de Hematología y Oncología Médica, Hospital Clínico Universitario de Valencia, Fundación Investigación Hospital Clinico de Valencia, Valencia, Spain.
authors.forename: Vicent M
authors.initials: VM
authors.lastname: Guillem
authors.forename: Cristina
authors.initials: C
authors.lastname: Arbona
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Hernández-Boluda
authors.forename: María José
authors.initials: MJ
authors.lastname: Terol
authors.forename: Rosa
authors.initials: R
authors.lastname: Goterris
authors.forename: Carlos
authors.initials: C
authors.lastname: Solano
authors.forename: Mar
authors.initials: M
authors.lastname: Tormo
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D005838:Genotype; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006801:Humans; D053208:Kaplan-Meier Estimate; D008223:Lymphoma / Q000235:genetics* / Q000401:mortality / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D016609:Neoplasms, Second Primary / Q000209:etiology / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012307:Risk Factors; D014182:Transplantation, Autologous; D016896:Treatment Outcome; D000076105:X-ray Repair Cross Complementing Protein 1; D055815:Young Adult
chemical_list: D004268:DNA-Binding Proteins; D000076105:X-ray Repair Cross Complementing Protein 1; C000619371:XRCC1 protein, human