关键词: 单核苷酸多态性, 三阴性乳腺癌, BRCA1基因, BRCA1相关蛋白复合物A

Abstract: Background and purpose: The mutation of BRCA1 gene is widely acknowledged to be related to the incidence of triple-negative breast cancer (TNBC). The aim of this study was to investigate the association between TNBC and single nucleotide polymorphisms (SNPs) of BRCA1-associated genes. Methods: This study investigated the associations between the BRCA1-A complex genes and risk of developing TNBC in a case-control study of Chinese Han Women population including 414 patients with TNBC and 354 cancer-free controls diagnosed in the Fudan University Shanghai Cancer Center during 2008-2011. This study also detected 37 common variants in Abraxas, BRE, Rap80, NBA1 and BRCC36 genes encoding the BRCA1-A complex and evaluated their genetic susceptibility to the risk of TNBC. An additional cohort with 652 other types of breast cancer (non-TNBC) cases and 890 controls were used to investigate the associations between TNBC-specific SNPs genotype and non-TNBCs susceptibility. Results: This study found that rs7250266 in the promoter region of NBA1 confers a decreased risk to TNBC (P<0.01). Compared with CC genotype, women with the GC genotype (OR=0.70, 95%CI: 0.51-0.97) and GG genotype (OR=0.48, 95% CI: 0.21-1.07) had a lower risk of developing TNBC (P=0.03). In addition, the haplotypes containing two polymorphisms rs7250266 and rs2278256 were associated with a lower chance of TNBC development. In the second part of the study, the result showed that there was no difference in rs7250266 expression between non-TNBC and normal people (0.19 vs 0.18, P=0.85).Conclusion: Genetic variants in NBA1 may be an important genetic determinant of TNBC susceptibility in Chinese women.

Key words: Single nucleotide polymorphisms, Triple-negative breast cancer, BRCA1 gene, BRCA1-A complex