Association of the Arg194Trp and the Arg399Gln polymorphisms of the XRCC1 gene with risk occurrence and the response to adjuvant therapy among Polish women with breast cancer.

Background: The XRCC1 gene encoding the X-ray cross-complementing group 1 protein (XRCC1) is involved in the base excision repair (BER) pathway.

Methods: The aim of this study was to investigate an association of the Arg194Trp and Arg399Gln polymorphisms of the XRCC1 gene with a risk of breast cancer occurrence and the response to adjuvant treatment among Polish women. Overall survival (OS) and disease-free survival (DFS) were investigated in groups of patients with breast cancer treated with (1) all types of adjuvant therapy, (2) concomitant radiotherapy and chemotherapy, (3) chemotherapy alone, or (4) radiotherapy alone. Polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) was used to evaluate the genotype distribution of the XRCC1 gene among 185 patients with breast cancer and 205 female controls.

Results: We showed a higher risk of breast cancer occurrence for the Trp allele and the Arg194Trp genotype of the XRCC1 gene. However there was no significant difference in distribution of the Arg399Gln genotype of XRCC1 between patients and the control group. In the patient subgroup treated with adjuvant therapy, Kaplan-Meier survival analysis showed a significantly higher OS as well as DFS for carriers of the Gln399Gln genotype when compared with carriers of the Arg399Gln and Arg399Arg genotypes. The Gln399Gln genotype was associated with a significantly higher DFS in the subgroup of patients treated with chemotherapy alone or with concomitant radiotherapy and chemotherapy.

Conclusion: We suggest that the polymorphism of the XRCC1 gene may be considered a predictive factor associated with the risk of occurrence and the survival outcome in breast cancer among Polish women.