Yang Li-Min, Li Xiu-Hua, Bao Cui-Fen
Department of Orthopaedics, The First Affiliated Hospital of Liaoning Medical College, Jinzhou, China.
Asian Pac J Cancer Prev. 2012;13(11):5883-6. doi: 10.7314/apjcp.2012.13.11.5883.
Osteosarcoma is the most common primary bone malignancy in children and adolescents, and its clinical outcome is poor. We evaluated the influence of GSTP1, ERCC1 and ERCC2 polymorphisms on response to chemotherapy among osteosarcoma patients, and the significnace of these genes for prognosis. A total of 187 patients with osteosarcoma were administered methotrexate, cisplatin/adriamycin, actinomycin D, cyclophosphamide, or vincristine. GSTP1, ERCC1 and ERCC2 polymorphisms were genotyped by PCR-RFLP assay. The results showed the average survival time of 187 patients were 38.4 months. Some 97 patients showed response to neoadjuvant chemotherapy. The GSTP1 Val and ERCC2 A/A genotypes had significantly higher rates of response to chemotherapy, with adjusted OR (95% CI) of 2.19 (1.15-6.21) and 2.88 (1.14-13.3). Individuals with the ERCC2 A/A genotype were likely to have a lower risk of death from oseosarcoma, and the adjusted HR was 0.32 (0.13-0.95). Our study indicated that GSTP1 and ERCC2 Lys751Gln polymorphisms might be candidate pharmacogenomic factors to be explored in the future to identify osteosarcoma patients who might benefit from chemotherapy.
骨肉瘤是儿童和青少年中最常见的原发性骨恶性肿瘤，其临床预后较差。我们评估了GSTP1、ERCC1和ERCC2基因多态性对骨肉瘤患者化疗反应的影响，以及这些基因对预后的意义。共有187例骨肉瘤患者接受了甲氨蝶呤、顺铂/阿霉素、放线菌素D、环磷酰胺或长春新碱治疗。通过PCR-RFLP分析对GSTP1、ERCC1和ERCC2基因多态性进行基因分型。结果显示，187例患者的平均生存时间为38.4个月。约97例患者对新辅助化疗有反应。GSTP1 Val和ERCC2 A/A基因型对化疗的反应率显著更高，调整后的OR（95%CI）分别为2.19（1.15 - 6.21）和2.88（1.14 - 13.3）。具有ERCC2 A/A基因型的个体骨肉瘤死亡风险可能较低，调整后的HR为0.32（0.13 - 0.95）。我们的研究表明，GSTP1和ERCC2 Lys751Gln基因多态性可能是未来有待探索的候选药物基因组学因素，以识别可能从化疗中获益的骨肉瘤患者。
