ERCC1, XRCC1 and GSTP1 Single Nucleotide Polymorphisms and Survival of Patients with Colon Cancer Receiving Oxaliplatin-Based Adjuvant Chemotherapy

Abstract

Background: While single nucleotide polymorphisms (SNP) in genes involved in DNA repair or drug metabolism have been shown to influence survival of metastatic colon cancer patients treated with FOLFOX, data on adjuvant setting are scarce.Methods: This study evaluated the correlation between disease-free survival (DFS) of 210 unselected stage III colon cancer patients receiving FOLFOX chemotherapy, and ERCC1-118 (rs11615, c.354T>C), XRCC1-399 (rs25487, c.1196G>A) and GSTP1-105 (rs1695, c.313A>G) polymorphisms. SNP were determined on tumor DNA using a PCR-based RFLP technique.Results: In univariate analysis, a trend towards longer DFS was observed for ERCC1 (C/T + T/T) versus (C/C) (HR=2.29; p=0.06), and XRCC1 (A/A) versus (G/G + G/A) (HR=1.61; p=0.16), but not for GSTP1 genotypes; a statistically significant p value was obtained when combining ERCC1 and XRCC1 favorable genotypes (0 versus ≥ 1 favorable genotypes, HR=2.42; p=0.02). After adjustment on tumor stage, lymph node ratio and differentiation grade, multivariate analysis showed that combining ERCC1 and XRCC1 genotypes gave a p value slightly above the threshold for statistical significance (HR=2.03; p=0.06), which was lower than for tumor stage, lymph node ratio or differentiation grade.Conclusion: The association of ERCC1 and XRCC1 polymorphisms may influence the prognosis of stage III colon cancer patients treated with FOLFOX adjuvant chemotherapy. Yet, these findings need to be confirmed in independent prospective studies.

ERCC1 expression in patients with colorectal cancer: a pilot study

“…In accordance with the current study, one CRC study reported a higher incidence of the C/T genotype, with 44% as compared to C/C (24%) and T/T (32%). [12] However, another reported that the frequencies of C/C, C/T, and T/T genotypes were 47.6%, 39.9% and 12.5%, respectively in Asian patients, very similar to previous reports in Caucasian populations. [4,13] In the present study, it was found that there was positive ERCC1 protein expression in 72% of CRC patients.…”

Correlation analysis between polymorphism of GSTP1, XPD and XRCC1 gene in esophageal carcinoma patients and treatment efficiency of cisplatin chemo-therapy

“…Similar reports can be found in a meta-analysis conducted by Gu et al [10], who showed the correlation between XRCC1 Arg399Gln polymorphism and efficacy of platinum drug in treating NonSmall Cell Lung Cancer (NSCLC). Similar observations have been found in the treatment of colon cancer [14,22] and ovarian carcinoma [23] using platinum drugs. Kim et al also found the correlation between polymorphism of Arg399Gln and GSTP1 Ile105Val locus with treatment efficacy of platinum on colorectal carcinoma [24].…”

“…Repair function related with platinum drug resistance is mainly consisted of nucleotide incision and base removal/repairmen [7][8][9]. Current findings revealed that the repair potency of human X-ray Repair CrossComplementing gene 1 (XRCC1) was correlated with Single Nucleotide Polymorphism (SNP) at 399 th locus, thus affecting chemotherapy efficiency of platinum based drugs [10][11][12][13][14]. Xeroderma pigmentosum group D (XPD) gene facilitates DNA repair by denaturing damaged site.…”

GSTP1 Ile105Val and XRCC1 Arg399Gln gene polymorphisms contribute to the clinical outcome of patients with advanced non-small cell lung cancer

“…Previous studies have reported that glutathione S-transferase P1 (GSTP1) and X-ray repair cross-complementing group 1 (XRCC1) genetic variations may influence the efficacy of chemotherapy in various cancers, such as colon cancer, gastric cancer, and ovarian cancer (Khrunin et al, 2010;Ji et al, 2013;Lai et al, 2013;Zaanan et al, 2014). Currently, many studies reported the role of GSTP1 and XRCC1 genetic polymorphisms in the clinical outcome of NSCLC, but the results are inconclusive.…”