XRCC1 and ERCC1 polymorphisms are related to susceptibility and survival of colorectal cancer in the Chinese population

Abstract

Excision repair cross complementing group 1 (ERCC1) and X-ray repair cross-complementing groups 1 (XRCC1) are DNA repair enzymes. Polymorphisms in DNA repair genes may be important factors affecting cancer susceptibility, prognosis and therapy outcome. The purpose of this study was to investigate the correlation of ERCC1 and XRCC1 polymorphisms with colorectal cancer (CRC) risk, and explore the effect of polymorphisms on event-free, overall survival and oxaliplatin-based therapy in CRC patients. Genotyping was examined with the iMLDR technique. An unconditional logistic regression model was used to estimate the association of certain polymorphisms with CRC risk. The Kaplan-Meier method, log-rank test and Cox regression model were employed to evaluate the effects of polymorphisms on survival analysis. Results showed that Trp/Trp genotype of XRCC1 Arg194Trp and AA genotype of ERCC1 rs2336219 have a significantly increased risk of CRC; Trp allele of XRCC1 Arg194Trp and CC genotype of ERCC1 rs735482 were associated with lower response to oxaliplatin-based chemotherapy, a shorter survival and a higher risk of relapse or metastasis. 194Trp/280Arg/399Arg haplotype was associated with a significant resistance, and the ERCC1 protein expression was statistically higher in tumours with rs735482 CC genotype than with AA genotype. Our studies indicate that XRCC1 and ERCC1 polymorphisms probably affect susceptibility, chemotherapy response and survival of CRC patients.

XRCC1 Gene Polymorphisms and miR-21 Expression in Patients with Colorectal Carcinoma

“…Moreover, Dai et al [17] showed that the XRCC1 194Arg/Trp gene polymorphism is associated with increased risk for CRC, reduced chemotherapy response, and reduced survival. Another study conducted by Nissar et al [18] among a Kashmiri population found a significant impact of the Trp/Trp and Arg/Trp genotypes on the development of CRC.…”

Association of DNA repair gene variants with colorectal cancer: risk, toxicity, and survival

“…A number of single nucleotide polymorphisms (SNPs) in DNA repair genes have been known to affect cancer susceptibility, prognosis, and therapeutic outcomes [8]. Indeed, SNPs in drug-targeted genes [9], metabolizing enzymes [10], and DNA-repairing enzymes [11] have been linked to inter-individual differences in the efficacy and toxicity of numerous drugs.…”

“…Indeed, SNPs in drug-targeted genes [9], metabolizing enzymes [10], and DNA-repairing enzymes [11] have been linked to inter-individual differences in the efficacy and toxicity of numerous drugs. Excision repair cross-complementing group 1 (ERCC1) and 2 (ERCC2) and X-ray repair cross-complementing group 1 (XRCC1) are DNA repair enzymes which play important roles in nucleotide excision repair [8].…”

“…The ERCC1 and ERCC2 proteins are highly conserved enzymes [12] which participate in the key steps of nucleotide excision repair such as the damage recognition and removal of DNA lesions induced by substances such as platinum [8,13,14]. SNPs in the ERCC1 and ERCC2 genes might be used as valuable predictive factors for oxaliplatin-based chemotherapy [15].…”

Arg399Gln substitution in XRCC1 as a prognostic and predictive biomarker for prostate cancer: Evidence from 8662 subjects and a structural analysis

“…Malignant transformation of prostate cells is always associated with genetic alterations such as deletions, inversion and point mutations . The association between genetic factors such as several single nucleotide polymorphisms (SNPs) with various cancers such as PCa, leukemia, colorectal cancer, breast cancer, and so on, has been reported . Several lines of investigations have shown the relationship between SNPs of the genes involved in DNA repair and cancer susceptibility.…”