Background: Breast cancer 2 (BRCA2) is an important breast cancer-susceptibility gene. Promoter polymorphisms in BRCA2 may affect its transcription and be associated with cancer prognosis.
Methods: We identified five polymorphisms of the BRCA2 promoter region by in silico searching and direct sequencing: -254A/G (rs3092989), -908A/G (rs206117), -1134A/G (rs206115), -1144C/T (rs206116), and -1260CTTAGA/- (rs3072036). The -908A/G, -1134A/G, -1144C/T, and -1260CTTAGA/- polymorphisms were genotyped by direct sequencing in 491 breast cancer patients, and the -254A/G polymorphism was genotyped by Sequenom.
Results: The -1144C/T polymorphism was associated with clinical outcome. Carriers of the TT genotype had longer disease-free intervals (DFIs, P = 0.029), especially among patients with sporadic unilateral breast cancer (P = 0.010). Linkage disequilibrium (LD) analysis showed that all the five single nucleotide polymorphisms (SNPs) were in LD (D' > 0.8). Carriers of haplotypes containing the -1144T allele showed longer DFIs (P = 0.049), and the result was more significant in patients with sporadic unilateral cancer (P = 0.018). There were no significant associations between the other polymorphisms and DFI.
Conclusions: The results of this study suggest that homozygosity for the BRCA2 T(-1144) allele is associated with a longer DFI in Chinese women with breast cancer. Further functional studies are warranted to clarify this relationship.