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

The aim of this study was to investigate the role of common polymorphisms in the NER pathway genes in the tumorigenesis of osteosarcoma and in the response to DNA damaging therapies, such as cisplatin-based neoadjuvant therapy. XPD (rs13181 and rs1799793), XPG (rs17655), and ERCC1 (rs3212986 and rs11615) polymorphisms were analysed in a group of 130 homogenously-treated patients with high-grade osteosarcoma for association with event free survival (EFS) using Kaplan-Meier plots and log-rank test. A positive association was observed between both XPD SNPs and an increased EFS (HR= 0.34, 95% 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 to wild type patients (OR=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