Nucleotide excision repair gene variants and association with survival in osteosarcoma patients treated with neoadjuvant chemotherapy

Abstract

The aim of this study was to investigate the role of common polymorphisms in the nucleotide excision repair pathway genes in the tumorigenesis of osteosarcoma and in the response to DNA damaging therapies, such as cisplatin-based neoadjuvant therapy. Excision repair cross-complementing (ERCC) group 2 (XPD; rs13181 and rs1799793), group 5 (XPG; rs17655) and group 1 (XPA; rs3212986 and rs11615) polymorphisms were analyzed in a group of 130 homogenously treated patients with high-grade osteosarcoma, for association with event-free survival (EFS), using the Kaplan-Meier plots and log-rank test. A positive association was observed between both XPD single-nucleotide polymorphisms and an increased EFS (hazards ratio (HR) = 0.34, 95% confidence interval (CI) 0.12-0.98 and HR = 0.19, 95% CI 0.05-0.77, respectively). We had also performed a case-control study for relative risk to develop osteosarcoma. Patients carrying at least one variant allele of XPD rs1799793 had a reduced risk of developing osteosarcoma, compared with wild-type patients (odds ratio = 0.55, 95% CI 0.36-0.84). This study suggests that XPD rs1799793 could be a marker of osteosarcoma associated with features conferring either a better prognosis or a better outcome after platinum therapy, or both.

Figure 1

XPD 35931A>C (rs13181) genotype curve's: ___AA vs. _ _AC vs. __ _ __CC

Figure 2

XPD 23591G>A (rs1799793) genotype curve's: ___GG vs. _ _GA vs. __ _ __AA

Figure 3

The curves represent the increased number of variant alleles for combination of XPD rs13181 and XPD rs1799793: ____ N=O (none variant alleles), __ __ __ N=1 (one variant allele of XPD rs13181 or XPD rs1799793), __ _ __ N=2 (two variant alleles among XPD rs13181 and/or XPD rs1799793), ____ _ ____N=3 (three variant alleles among XPD rs13181 and/or XPD rs1799793), _ _ _ _N=4 (all four variant alleles).