Susceptibility to Breast Cancer and Intron 3 Ins/Del Genetic Polymorphism of DNA Double-Strand Break Repair Gene XRCC4

BACKGROUND: Since genetic variations in X-ray cross-complementing group 4 (XRCC4; OMIM: 194363) repair gene might be associated with a reduction in cellular DNA repair capacity, it is hypothesized that XRCC4 Ins/Del (I/D) polymorphism (in intron 3 of the gene; rs28360071) may be a risk factor for breast cancer. Therefore, the present case-control study was carried out. METHODS: The present case-control study included 407 females with breast cancer and a total of 394 healthy females from the general population matched with patients according to age. Genotypic analysis for the XRCC4 I/D polymorphism was performed by PCR. In order to investigate the effect of XRCC4 I/D polymorphism on age at diagnosis of breast cancer, the Kaplan–Meier survival analysis and the Cox proportional hazards regression model were used. RESULTS: Based on the present case-control study, the ID (OR=0.95, 95% CI: 0.69–1.31, P=0.781) and DD (OR=1.24, 95% CI: 0.84–1.83, P=0.274) genotypes were not associated with breast cancer risk compared with the II genotype. Based on the Cox regression model, there was significant association between genotypes of I/D polymorphism and age at diagnosis of breast cancer (ID+DD vs II; HR=0.79, 95% CI: 0.64–0.98, P=0.036). CONCLUSION: Although there was no significant association between XRCC4 I/D polymorphism and risk of breast cancer, patients having the II genotype have lower age at diagnosis in comparison with patients having ID+DD genotypes.