Association Between Ercc1 And Xpf Polymorphisms And Risk Of Extrahepatic Cholangiocarcinoma

Background: Several risk factors, including primary sclerosing cholangitis, liver fluke infection, HBV/HCV infection, biliary malformations, and hepatolithiasis have been identified for developing cholangiocarcinoma (CCA). However, more than 85% of patients with extrahepatic cholangiocarcinoma (ECCA) have no explicit risk factors. Polymorphisms in excision repair cross-complementing group 1 (ERCC1) and xeroderma pigmentosum group F (XPF) could affect DNA repair capability. In this study, we studied the influence of ERCC1-XPF polymorphisms on ECCA incidence. Methods: The present study included 127 patients diagnosed of ECCA and 145 normal controls. The Genotypes of ERCC1-XPF were detected by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) method, and then the products were sent for sequencing. Results: The ERCC1 rs3212986 C > A genotype AC+AA frequency was significantly different between the cases and controls (AC+AA, OR: 1.68, 95% CI: 1.04-2.72) comparing with genotype CC. The ERCC1 rs2298881 A > C genotype CC frequency was significantly different between the cases and controls (CC, OR: 2.15, 95% CI: 1.01-4.56) comparing with genotype AA. No associations with risk of ECCA were found for other three SNPs (ERCC1 rs11615, XPF rs6498486 and XPF rs2276466). Subgroup analysis showed that an extra increased risk in smokers was observed both in ERCC1 rs3212986 AC+AA genotype (OR: 2.75, 95% CI: 1.04-7.30) and rs229888 AC+CC genotype in smokers (OR: 3.22, 95% CI: 1.19-8.71). Conclusions: The present study indicated that rs3212986 C > A and rs2298881 A > C polymorphisms of ERCC1 were associated with an increased risk of ECCA, especially in smokers. It would be necessary to confirm these findings in a large sample size and multiethnic population study in future.