Prediction of polymorphisms in DNA repair genes on the prognosis of bone tumors with methotrexate, intravenous adriamycin and intra-arterial cisplatin chemotherapy

摘要

We investigate the relationship of SNPs in XRCC1, ERCC1 and ERCC2 to methotrexate intravenous adriamycin and intra-arterial cisplatin chemotherapy response and survival in bone cancer patients. 281 consecutive patients diagnosed with bone tumor between January 2003 to January 2005, and they were followed up until the end of January 2010. Polymorphisms in XRCC1Arg280His, XRCC1Arg399Gln, ERCC1 Asn118Asn, ERCC1 Gln504Lys, ERCC2 Asp312Asn and ERCC2 Lys751Gln were detected based upon Sequenom MassARRAY platform. All 281 patients were followed up until the end of January 2010. The median follow-up time was about 43.9 months. Our study showed a longer survival rate in XRCC1 399 Arg/Arg genotype than Gln/ Gln, and with a significant increased death risk (HR=0.46, 95%CI=0.31-0.96). For ERCC1 Asn118Asn, the variant genotype T/T was strongly significantly associated with a higher event free survival when compared with the wide-type C/C, with the adjusted OR (95% CI) of 0.33(0.15-0.97). ERCC2 751 A/A genotype showed increased the event free survival of osteosarcoma (HR=0.45; 95%CI=0.15-0.91), and T allele genotype of ERCC2 Lys751Gln was significantly associated with low risk of death from osteosarcoma (HR=0.53, 95%CI= 0.28-0.95). This study is the first time to report the ERCC1 and ERCC2 gene polymorphisms might well be useful as a surrogate marker of clinical outcome in bone cancer.