Association between ERCC1 and ERCC2 gene polymorphisms and chemotherapy response and overall survival in osteosarcoma

Abstract

ABSTRACT. We aimed to evaluate the influence of four SNPs in ERCC1 and ERCC2 on the response to cisplatin-based treatment and on clinical outcome in patients with osteosarcoma. We identified 186 patients with osteosarcoma diagnosed between April 2009 and April 2011 who were eligible for inclusion in our study. Genotyping of ERCC1 rs11615, rs3212986, and rs2298881; and ERCC2 rs1799793 and rs13181 was conducted by a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. By conditional logistic regression analysis, patients carrying the CC genotypes of ERCC1 rs11615 and rs2298881 were shown to be more likely to have good response to chemotherapy when compared with patients carrying wildtype genotypes; the ORs (95%CIs) were 2.56 (1.02-7.35) and 3.01 (1.07-9.71), respectively. By Cox regression analysis, individuals carrying the CC genotype of ERCC1 rs11615 were associated with longer overall survival time and decreased risk of death from osteosarcoma; the hazards 10146 Z.H. Cao et al. ©FUNPEC-RP www.funpecrp.com.br Genetics and Molecular Research 14 (3): 10145-10151 (2015) ratio (95%CI) was 0.32 (0.07-0.98). In summary, our results suggested that the ERCC1 rs11615 and rs2298881 polymorphisms play important roles in the response to chemotherapy mediated by the DNA repair pathway and in the clinical outcome of osteosarcoma.

Genetic polymorphisms in ERCC1 and ERCC2 genes are associated with response to chemotherapy in osteosarcoma patients among Chinese population: a meta-analysis

“…Then the remaining 76 articles were estimated for eligibility according to our inclusion and exclusion criteria. Finally six eligible articles [12–14, 17, 20, 21] were included in our meta-analysis. The flow diagram of study selection process and reasons for exclusion was represented in Fig.…”

“…The pooled odds ratios (ORs) were calculated for dominant model, recessive model, and allelic model for ERCC1 rs11615, ERCC2 rs1799793, and ERCC2 rs13181 polymorphisms, respectively. The evaluation of response to chemotherapy was identified as the previous relevant studies [12, 16, 17]. An OR > 1 refers less OS patients with poor response to chemotherapy occur in the reference group, and patients in reference group have higher response rate to chemotherapy.…”

“…A retrospective study showed that ERCC2 rs1799793, a DNA repair polymorphism, was a predictive factor for chemotherapy response in OS patients [11]. A study published on 2015 suggested that the polymorphism of ERCC1 rs11615 affected on the response to chemotherapy in OS treatment [12]. However, there is debate on the predictive value of SNPs in ERCC1 and ERCC2 genes for the response to chemotherapy for OS.…”

The association of XRCC1 polymorphism with osteosarcoma risk, clinicopathologic features, and prognosis in a Chinese Han population

“… 5 Genetic factors might play a key role in OS pathogenesis. To date, several previous studies have reported associations of DNA repair gene variants in biologically plausible pathways with OS risk, 6 – 10 such as ERCC1 , ERCC2 , APE, and so on . X-ray repair cross-complementing group 1 ( XRCC1 ) is a member of the DNA repair gene family, which is responsible for fixing DNA base damage and single-strand breaks through interacting with DNA components at the damage site.…”

rs1760944 Polymorphism in the APE1 Region is Associated with Risk and Prognosis of Osteosarcoma in the Chinese Han Population

“…Many factors are known to play an essential role in the development of OS, including environmental and genetic factor 14 . Hereditary factors have also been found to be significantly associated with OS, particularly regarding gene polymorphisms in the DNA repair systems such as ERCC , XPD , and GST 15 – 17 . However, until now, there has been a scarcity of data regarding the association of APE1 polymorphism with OS patients.…”