BRCA2 promoter polymorphism is associated with breast cancer prognosis in Chinese women

• Published in: Chinese medical journal 2014, Vol.127 (11), p.2012-2015
• Main Authors: Liu, Lu, Fang, Yi, Fan, Jianlin, Hu, Jianming, Xu, Xiaoting, Jin, Xiaohong, Wang, Xiuzhen, Deng, Min, Wang, Jing, Liu, Wei
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Asian Continental Ancestry Group - genetics; BRCA2; Breast Neoplasms - genetics; Breast Neoplasms - pathology; Female; Genetic Predisposition to Disease - genetics; Genotype; Haplotypes; Humans; Linkage Disequilibrium; Middle Aged; Polymorphism, Single Nucleotide - genetics; Promoter Regions, Genetic - genetics; 中国; 乳腺癌; 单核苷酸多态性; 基因启动子区; 女性; 直接测序; 预后
• ISSN: 0366-6999; 2542-5641
• DOI: 10.3760/cma.j.issn.0366-6999.20130978

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.