Abstract P3-07-07: Single nucleotide polymorphisms of BRCA1-interacting genes are associated with triple-negative breast cancer in Chinese Han woman
Authors: Ling H , Hu X , Shao Z-M 
Published: August 2014

Abstract
Aims
The mutation of BRCA1 is reported to be linked to the onset of triple negative breast cancer (TNBC). However, the incidence of mutation of BRCA1 in Chinese woman is very low. Recent studies have identified genes that encode proteins that interact with BRCA1 as modifiers of BRCA1-associated breast cancer. We evaluated a comprehensive set of genes that encode most known BRCA1 interactors to evaluate the role of these genes as modifiers of TNBC risk in Chinese Han woman.
Methods
After a proven by IRB, totally 414 patients with TNBC treated in Fudan University Shanghai Cancer Center and 354 healthy women were recruited in this study. Written informed consents were obtained before their recruitment. The DNA from their peripheral blood were obtained. The single nucleotide polymorphisms (SNPs) investigated in this study were consisted of SNPs reported in literatures, SNPs in function region (exons, intron-exon binding regions, promoters and 5’UTR) with MAF larger than 0.05 and tag SNPs in intron. In addition, SNPs that showed significant deviations (&lt;0.05) from Hardy-Weinberg equilibrium among controls or call rate less than 0.95 in the study were also excluded. Finally, 37 SNPs from 5 BRCA1-associated genes (Abraxas, BRE, Rap80, BABAM1, BRCC36) were analyzed by Massarray system.
Results
An association was observed between TNBC risk and rs7250266 at BABAM1. The allelic frequency for the G-allele of rs7250266 was 0.19 in controls compared with 0.14 in patients, with significant difference. A comparison of genotyping frequency between cases and controls indicated that GC genotype of rs7250266 were associated with significantly decreased TNBC risk (OR of GC genotype 0.70, 95% CI 0.51-0.97, OR of GG genotype 0.48, 95% CI 0.21-1.07, P = 0.03). Under a dominant model, it's shown that women with genotypes GC/GG of re7250266 conferred approximately 33% decreased risk to the development of breast cancer (OR 0.67, 95% CI 0.49-0.92, P = 0.01). Another SNP at BABAM1, rs2278256 showed a borderline association with the risk of TNBC. It is also in one linkage disequilibrium (LD) block with rs7250266.
Two haplotypes at BABAM1 were demonstrated to be associated with a decrease risk of TNBC.
Haplotype Analysis to BABAM1SNPs Frequency*OR (95%CI)Prs7250266rs2278256rs144376330rs10403581rs3745185 CACAG0.5281.00 CGCAG0.1720.99 (0.75-1.32)0.97GGCCG0.1490.75 (0.56-0.99)0.04CACCA0.1221.14 (0.83-1.57)0.41GGCAG0.0150.34 (0.14-0.85)0.02CATAG0.0121.00 (0.38-2.58)0.99*Haplotypes with frequency &lt;1% were not analyzed
Conclusions
We investigated 37 SNPs in 5 BRCA1-associated genes and demonstrated the mutation of rs7250266 was associated with a decrease risk of developing TNBC in Chinese women. It's the first time this SNP was reported to be associated with breast cancer. Further analysis confirmed haplotypes with mutation of rs7250266 and rs2278256 had a lower risk of developing TNBC than other haplotypes.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P3-07-07.