Genetic polymorphisms in nucleotide excision repair pathway influences response to chemotherapy and overall survival in osteosarcoma.
We analyzed the role of genetic polymorphisms of six important NER pathway genes in response to chemotherapy and clinical outcome of osteosarcoma patients. A prospective study including 172 osteosarcoma patients was conducted between January 2009 and January 2011. The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used for ERCC1 rs11615 and rs2298881, ERCC2 rs13181 and rs1799793, ERCC4 rs1800067, ERCC5 rs1047768, XPA 1800975, and XPC rs2228000 and rs2228001 gene polymorphisms. By logistic regression analysis, TT genotype of ERCC1 rs11615 genetic polymorphism was significant correlated with poor response to chemotherapy when compared with wide-type genotype (OR=0.27, 95% CI=0.10-0.71). AC and CC genotype of ERCC1 rs2298881 were significantly associated with poor response to chemotherapy when compared with AA genotype (For AC genotype, OR=0.45, 95% CI=0.21-0.97; for CC genotype, OR=0.19, 95% CI=0.06-0.58). By Cox proportional hazards regression analysis, TT genotype of ERCC1 rs11615 and CC genotype of ERCC1 rs2298881 suffered a 3.16 and 3.57-fold increased hazards of death (For ERCC1 rs11615, HR=3.16, 95% CI=1.19-9.16; for ERCC1 rs2298881, HR=3.57, 95% CI=1.10-11.35). In conclusion, our findings suggest that ERCC1 rs11615 and ERCC1 rs2298881 genetic polymorphisms are significantly associated with poor response to chemotherapy and unfavourable survival of osteosarcoma.
Department of Traum Orthopedics, The Fifth Affiliated Hospital of Southern Medical University Guangzhou, China.
Yongjian
Y
Sun
Department of Traum Orthopedics, The Fifth Affiliated Hospital of Southern Medical University Guangzhou, China.
Yi
Y
Wu
Department of Traum Orthopedics, The Fifth Affiliated Hospital of Southern Medical University Guangzhou, China.
Weicheng
W
Li
Department of Traum Orthopedics, The Fifth Affiliated Hospital of Southern Medical University Guangzhou, China.
Zhen
Z
Kong
Department of Cardiothoracic Surgery, The Fifth Affiliated Hospital of Southern Medical University Guangzhou, China.
Xiaoming
X
Zou
D000293:Adolescent; D000328:Adult; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics* / Q000401:mortality; D016009:Chi-Square Distribution; D004260:DNA Repair / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D018450:Disease Progression; D018572:Disease-Free Survival; D004720:Endonucleases / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D053208:Kaplan-Meier Estimate; D016015:Logistic Models; D008297:Male; D015999:Multivariate Analysis; D016017:Odds Ratio; D012516:Osteosarcoma / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics* / Q000401:mortality; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
D000970:Antineoplastic Agents; D004268:DNA-Binding Proteins; C071447:ERCC1 protein, human; D004720:Endonucleases
NER pathway; osteosarcoma; overall survival; response to chemotherapy