Polymorphisms in the genes ERCC2, XRCC3 and CD3EAP influence treatment outcome in multiple myeloma patients undergoing autologous bone marrow transplantation.
Individual variations in the ability to cope with DNA damage by DNA repair may be essential for the response to chemotherapy, since cancer cells from patients with an effective DNA repair may survive treatment. We have studied the effect on time to treatment failure (TTF) and overall survival (OS) of polymorphism in the DNA repair genes ERCC1, ERCC2 and XRCC3, and in the apoptotic genes PPP1R13L and CD3EAP in 348 patients with multiple myeloma undergoing autologous bone marrow transplantation. Carriers of the variant C-allele of ERCC2 K751Q, the variant T-allele of XRCC3 T241M and the variant A-allele of CD3EAP G-21A had a 1.3-fold, 1.8-fold and 1.9-fold longer TTF, respectively, than homozygous wild type carriers (p = 0.006, p = 0.004, p < 0.001). The polymorphism CD3EAP G-21A also had significant effect on OS (p < 0.045). The polymorphism ERCC2 K751Q may to be related to sex, since the prolonged TTF was only seen in women (p = 0.001). Carriers of the combination of variant alleles of ERCC2 K751Q and XRCC3 T241M had 2.8-fold longer TTF (p = 0.0002). This indicates that suboptimal repair of both DNA mechanisms favors prolonged TTF and that polymorphism in ERCC2, XRCC3 and CD3EAP predicts the outcome for patients treated with autologous stem cell transplantation.
Vangsted
Annette
A
Department of Haematology, Herlev University Hospital of Copenhagen, DK-2730 Herlev, Denmark. anevan01@herlevhosp.kbhamt.dk
Gimsing
Peter
P
Klausen
Tobias W
TW
Nexø
Bjørn A
BA
Wallin
Håkan
H
Andersen
Pernille
P
Hokland
Peter
P
Lillevang
Søren T
ST
Vogel
Ulla
U
D000368:Aged; D000483:Alleles; D014408:Biomarkers, Tumor / Q000235:genetics*; D016026:Bone Marrow Transplantation; D004268:DNA-Binding Proteins / Q000235:genetics*; D003718:Denmark; D005260:Female; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000235:genetics / Q000601:surgery*; D015999:Multivariate Analysis; D020641:Polymorphism, Single Nucleotide; D012318:RNA Polymerase I; D014182:Transplantation, Autologous; D016896:Treatment Outcome; D051759:Xeroderma Pigmentosum Group D Protein / Q000235:genetics*
D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; C110901:X-ray repair cross complementing protein 3; C119975:POLR1G protein, human; D012318:RNA Polymerase I; D051759:Xeroderma Pigmentosum Group D Protein; C497292:ERCC2 protein, human