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.
目的探讨BRCA2基因11号外显子多态性与乳腺癌预后的相关性。方法采用限制性片段长度多态性聚合酶链反应技术(PCR-restriction fragment length polymorphism,PCR-RFLP)、高分辨率熔解曲线技术和直接测序法对159例散发性乳腺癌患者外周血中基因组DNA进行等位基因分型,并运用Kaplan-Meier法进行生存分析。结果 N991D多态位点与乳腺癌患者的无病生存期相关联,携带ND基因型的患者无病生存期较长(P=0.033),与临床病理特征无明显相关性。BRCA2基因M784V多态性在中国人群中罕见。结论中国人群的遗传背景与外国人群存在差异性。BRCA2基因N991D多态性与乳腺癌预后存在相关性。
