XRCC1 Arg194Trp and Arg399Gln polymorphisms and risk of extrahepatic cholangiocarcinoma: a hospital-based case-control study in China

Background: Extrahepatic cholangiocarcinoma (ECCA) is a rare but devastating malignancy. Up to 90% of patients presenting with ECCA have no identifiable risk factors. The base excision repair (BER) pathway has a principal role in the repair of mutations caused by oxidized or reduced bases. The XRCC1 is one of the key proteins in the BER pathway. In this study, we investigated the influence of XRCC1 Arg194Trp and Arg399Gln polymorphisms on ECCA incidence. Methods: The study included 189 ECCA patients and 216 controls. Genotypes were detected by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) method. Results: For codon 194, the genotype frequencies of C/C, T/C and T/T were 51.3, 43.4 and 5.3%, respectively, in the ECCA cases compared with 54.2, 38.9 and 6.9%, respectively, in the controls. No statistically significant differences were observed in the genotype frequencies of codon 194 between the two groups compared to the control (TC, OR: 0.85, 95% CI: 0.57-1.28, TT, OR: 1.24, 95% CI: 0.54-2.89, TC+TT, OR: 0.89, 95% CI: 0.60-1.32). For codon 399, the genotype frequencies of G/G, G/A and A/A were 54.0, 37.0 and 9.0%, respectively, in the ECCA cases compared with 56.1, 39.8 and 4.1%, respectively, in the controls. No statistically significant differences were observed in the genotype frequencies codon 399 between the two groups compared to the control (GA, OR: 1.04, 95% CI: 0.69-1.56, AA, OR: 0.45, 95% CI: 0.19-1.04, GA+AA, OR: 0.92, 95% CI: 0.62-1.36). Meanwhile, no statistically significant differences were found in the haplotype and risk of developing ECCA compared to the control (CA, OR: 0.83, 95% CI: 0.49-1.39, TG, OR: 0.96, 95% CI: 0.58-1.60, TA, OR: 0.83, 95% CI: 0.38-1.82). Conclusion: The present study suggested that Arg194Trp and Arg399Gln polymorphism in the DNA repair gene XRCC1 was not statistically associated with risk of ECCA. It would be necessary to confirm these findings in a large sample size and multiethnic population study in future.