Association between XRCC1 and ERCC1 single-nucleotide polymorphisms and the efficacy of concurrent radiochemotherapy in patients with esophageal squamous cell carcinoma

Abstract

The aim of the present study was to investigate the association between single-nucleotide polymorphisms (SNPs) in X-ray repair cross-complementing 1-399 (XRCC1-399) or excision repair cross-complementation group 1-118 (ERCC1-118) and the short-term efficacy of radiochemotherapy, tumor metastasis and relapse, as well as the survival time in patients with esophageal squamous cell carcinoma (ESCC). TaqMan probe-based quantitative polymerase chain reaction (qPCR) was conducted to examine the levels of XRCC1-399 and ERCC1-118 SNPs in the peripheral blood of 50 patients with pathologically confirmed ESCC. In addition, the associations between different genotypes and short-term therapeutic efficacy [the complete remission (CR) rate], tumor metastasis and relapse, as well as the survival time following concurrent radiochemotherapy, were determined. A total of 50 ESCC patients who received concurrent radiochemotherapy were enrolled. It was found that the short-term therapeutic efficacy (CR rate) was higher in the group of patients carrying the homozygous mutation of XRCC1-399 (A/A genotype) than in the group of patients without the XRCC1-399 mutation (G/G genotype). In addition, the CR rate was significantly increased in patients carrying one or two ERCC1-118 C alleles (C/C or C/T genotype) compared with patients lacking the C allele (T/T genotype). The differences were statistically significant (A/A vs. G/G, P=0.014; TT vs. C/T+C/C, P=0.040). During the follow-up period, the group of patients carrying the homozygous mutation of XRCC1-399 (A/A genotype) exhibited a markedly reduced risk of metastasis and relapse compared with the group of patients carrying non-mutated XRCC1-399 (G/G genotype; P=0.031). By contrast, ERCC1-118 SNP was not associated with the risk of metastasis and recurrence (P>0.05). The combined results of univariate and multivariate Cox regression analysis showed that the SNP in ERCC1-118 was closely associated with survival time. The mean survival time was significantly prolonged in patients carrying 1 or 2 C alleles (C/C or C/T genotype) compared with patients lacking the C allele (T/T genotype) [T/T vs. C/C, HR=12.96, 95% confidence interval (CI)=3.08-54.61, P<0.001; TT vs. C/T+C/C, HR=11.71, 95% CI=3.06-44.83, P<0.001]. However, XRCC1-399SNP had no effect on survival time (P>0.05). XRCCl-399 SNP was associated with the short-term therapeutic efficacy (the CR rate) and tumor metastasis/relapse in ESCC patients who received the docetaxel plus cisplatin (TP) regimen-based concurrent radiochemotherapy. By contrast, ERCC1-118 SNP was significantly associated with the short-term therapeutic efficacy (the CR rate) and survival time in ESCC patients who received TP regimen-based concurrent radiochemotherapy.

Keywords: X-ray cross-complementing group 1; concurrent radiochemotherapy; esophageal cancer; excision repair cross-complementing group 1; single nucleotide polymorphism.

Figure 1.

Comparison of the survival time of the XRCC1-399 genotypes (G/G, G/A or A/A). XRCC1, X-ray repair cross-complementing 1. Compared with the non-mutated group (G/G genotype), the survival time of patients carrying the heterozygous XRCC1-399 mutation (G/A genotype) and the homozygous mutation of XRCC1-399 (A/A genotype) was extended. However, the difference was not statistically significant (P=0.283).

Figure 2.

Comparison of the survival time of XRCC1-399 genotypes (G/G or G/A+A/A). XRCC1, X-ray repair cross-complementing 1. The mutated XRCC1-399 group (G/A+A/A genotypes) included patients with either G/A or A/A genotype. Compared with the non-mutated group (G/G genotype), the median survival time was prolonged. However, the difference was not statistically significant (P=0.208).

Figure 3.

Comparison of the survival time of ERCC1-118 genotypes (C/C, C/T or T/T). ERCC1, excision repair cross-complementing group 1. Compared with patients lacking the C allele (T/T genotype), the mean survival time was prolonged in patients carrying one or two C alleles (C/C or C/T genotype). The difference was statistically significant (P<0.001).

Figure 4.

Comparison of the survival time of ERCC1-118 genotypes (T/T or C/C+C/T). ERCC1, excision repair cross-complementing group 1. Compared with patients lacking the C allele (T/T genotype), the mean survival time was prolonged in the total of patients carrying one or two C alleles (C/C+C/T genotype). The difference was statistically significant (P<0.001).