Abstract
SNPs of ERCC1 and ERCC2 genes have been found to be associated with response to platinum therapy in different clinical settings. In the current study, we investigated the relationship of SNPs in ERCC1 and ERCC2 to cisplatin response and survival in osteosarcoma patients. 267 consecutive patients diagnosed with osteosarcoma between January 2003 to January 2005 were followed up until the end of January 2010. ERCC1 Asn118Asn, ERCC1 Gln504Lys, ERCC2 Asp312Asn and ERCC2 Lys751Gln polymorphisms were detected based upon the Sequenom MassARRAY platform. For ERCC1 Asn118Asn, the variant genotype T/T was strongly significantly associated with a higher event free survival when compared with the wild-type C/C, with an adjusted OR (95% CI) of 0.39 (0.14-0.95). ERCC2 751 A/A genotype showed increased event free survival of osteosarcoma (HR=0.44; 95%CI=0.10-0.87). However, we did not find significant association of ERCC1 Gln504Lys and ERCC2 Asp312Asn polymorphisms with prognosis of osteosarcoma. We first report associations of four SNPs, ERCC1 Asn118Asn, ERCC1 Gln504Lys, ERCC2 Asp312Asn and ERCC2 Lys751Gln, with risk of death from osteosarcoma in a Chinese population, indicating ERCC1 118T/T and ERCC2 A/A may be used as surrogate markers for clinical outcome of osteosarcoma treatment with cisplatin.
Highlights
Cancer that originates in the bone, termed primary bone cancer, is rare and typically occurring during the children and adolescent growth spurt, with a second smaller peak in the elderly
We investigated the relationship of SNPs in ERCC1 and ERCC2 to cisplain response and survival in osteosarcoma patients
Our study firstly published the associations of ERCC1 and ERCC2 polymorphisms and the prognosis of primary malignant osteosarcoma in Chinese populations, and implied ERCC1
Summary
Cancer that originates in the bone, termed primary bone cancer, is rare and typically occurring during the children and adolescent growth spurt, with a second smaller peak in the elderly. Osteosarcoma is one of the most frequent bone tumors, with a 3-5/105 population per year worldwide, but this tumor accounted for about 6% of all cancer diagnosed under the age of 20 years (American Cancer Society et al, 2007; Lu et al, 2011). The five years survival of osteosarcoma is below 20% after surgery, but the chemotherapy after surgery have dramatically improved the survival to 55% to 70% after years (Le et al, 2007). Patients who have similar clinical characteristics usually showed variable response rate to chemotherapy, with inferior 5-year survival of 40% to 70% (Le et al, 2007). This implies the therapeutic efficacy has a remarkable interindividual variability
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