Association between common polymorphisms in ERCC gene and prognosis of osteosarcoma in patients treated with chemotherapy: a meta-analysis

Chunpu Li,1,2,* Xin Yu,1,* Dongmei Guo,3,4 Guanhua Liu,5 Kaigang Zhang,1 Qingliang Teng,3 Hai Lin4 1Department of Orthopedics, Taian City Central Hospital, Taian, China; 2Department of Orthopedics, Qilu Hospital, Shandong University, Jinan, China; 3Department of Hematology, Taian City Central Hospital, Taian, China; 4Department of Animal Science, College of Animal Science and Veterinary Medicine, Shandong Agricultural University, Taian, China; 5Department of Nutrition and Food Hygiene, School of Public Health, Taishan Medical University, Taian, China *These authors contributed equally to this work Purpose: Some previous studies have sought to investigate the roles of excision repair cross complementation group 1 (ERCC1), ERCC2, ERCC4, and ERCC5 gene polymorphisms in the prognosis of osteosarcoma patients. However, their results were inconclusive. Here, we performed a meta-analysis to determine the strength of the association between eight polymorphisms in the ERCC genes (rs11615, rs3212986, rs2298881, rs13181, rs1799793, rs1800067, rs2296147, and rs1047768) and prognosis of osteosarcoma patients treated with chemotherapy. Materials and methods: We retrieved the relevant studies from PubMed, Embase, and Web of Science in human osteosarcoma published prior to July 2017. Primary outcomes included overall survival (OS) and event-free survival, expressed by hazard ratios (HRs) with their corresponding 95% CIs. STATA software (version 12.0) was utilized to perform data synthesis. Results: A total of 13 eligible follow-up studies involving 2,303 patients met all the inclusion criteria, conducted in two populations of ethnic descent: 11 Asians and two Caucasians. In the present meta-analysis, we demonstrated that the homozygous variant genotypes in ERCC2 rs1799793 and ERCC5 rs2296147 were significantly associated with OS in osteosarcoma (TT vs GG for rs1799793: HR = 0.62, 95% CI = 0.41–0.93, Pheterogeneity = 0.310, I2 = 15.3%, P = 0.020; TT vs CC for rs2296147: HR = 0.42, 95% CI = 0.23–0.78, Pheterogeneity = 0.708, I2 = 0.0%, P = 0.006). In addition, no evidence of association was observed between prognosis in osteosarcoma and ERCC1 rs11615, ERCC1 rs3212986, ERCC1 rs2298881, ERCC2 rs13181, ERCC4 rs1800067, and ERCC5 rs1047768 polymorphisms. Conclusion: Our meta-analysis indicated that TT genotype in the ERCC2 rs1799793 and ERCC5 rs2296147 might prolong the survival time of patients with osteosarcoma, suggesting that the rs1799793 and rs2296147 polymorphisms can be used as predictors for prognosis of osteosarcoma patients treated with chemotherapy. Keywords: ERCC2 rs1799793, ERCC5 rs2296147, polymorphisms, osteosarcoma, chemotherapy, prognosis, meta-analysi