Polymorphism of XRCC1 (at codon 399) and susceptibility to breast cancer, a meta-analysis of the literatures.

The X-ray repair cross-complementation group 1 (XRCC1) protein plays an important role in base excision repair. Several polymorphisms in the XRCC1 gene have been described, including Arg399Gln. Previous studies investigating the association between genetic polymorphism of Arg399Gln XRCC1 and risk of breast cancer have provided inconsistent results. A meta-analysis was conducted to investigate the association between common genetic variant in the XRCC1 gene (exon 10, Arg399Gln) with breast cancer risk. We identified 36 eligible studies, in relation to the Arg399Gln polymorphism of XRCC1 and risk of breast cancer. These studies comprised of 43,716 subjects (20,837 patients and 22,879 controls). We first estimated the risk of the genotypes Arg/Gln and Gln/Gln compared with the wild-type Arg/Arg homozygote, and then evaluated the risk of Gln/Gln versus (Arg/Gln+Arg/Arg) and (Gln/Gln+Arg/Gln) versus Arg/Arg, which assumed recessive and dominant effects, respectively, of the variant 399Gln allele. There was significant heterogeneity between studies. The overall ORs showed that the breast cancer risk were not associated with the XRCC1 genotypes. The heterogeneity between studies decreased dramatically when studies stratified into Asian and Western countries. There was significant association between the polymorphism of XRCC1 and breast cancer risk among studies of Asian countries. In Asian countries the Arg/Gln versus Arg/Arg (OR = 0.98, 95% CI: 0.88-1.10) and Gln/Gln+Arg/Gln versus Arg/Arg (OR = 1.05, 95% CI: 0.95-1.18) were not associated with increased risk of breast cancer. On the other hand, both Gln/Gln versus Arg/Arg (OR = 1.46, 95% CI: 1.19-1.79) and Gln/Gln versus Arg/Gln+Arg/Arg (OR = 1.49, 95% CI: 1.22-1.81) increased the risk. Therefore, it could be concluded that 399Gln allele might act as a recessive allele in its association with breast cancer risk.