Abstract 2550: A genome-wide association study of breast cancer survival according to molecular subtype in Korean women.

Abstract

Abstract Background: Breast cancer is heterogeneous disease according to ethnicity and molecular subtype. In this study, we conducted a genome-wide association study (GWAS) to evaluate the association between susceptibility loci and breast cancer survival by the molecular subtypes which were classified into four subtypes based on estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) in Korean women. Methods: Analyses included 2,023 invasive breast cancer patients, comprised of ER/PR+ and HER2- (N=1,006), ER/PR+ and HER2+ (N=245), ER/PR- and HER2+ (N=226), ER/PR- and HER2- (N=279), and unknown subtype (N=267), from Seoul Breast Cancer Study (SeBCS). For analyses, 555,117 SNPs were genotyped using Affymetrix SNP Array 6.0 and 2,416,663 SNPs were imputated based on HapMap Phase II (release 22). Cox proportional hazard models adjusted for age, recruited centers, and TNM stage were used to test the association of these SNPs with disease-free survival (DFS) and overall survival (OS) by molecular subtype. Results: With median follow-up periods of 3.8 years in DFS and 4.0 years in OS, there was significant difference in survival between molecular subtypes tested by log-rank (P<0.0001, Log-rank test). Compared to ‘ER/PR+ and HER2-‘, ‘ER/PR- and HER2+’ and ‘ER/PR- and HER2-’ were associated with a poorer prognosis (HRER/PR- and HER2+ (95% CI)=2.00 (1.35-2.97), HRER/PR- and HER2-=2.37 (1.70-3.29) in DFS and HRER/PR- and HER2+=2.54 (1.50-4.30), HRER/PR- and HER2-=2.59 (1.65-4.08) in OS). By molecular subtypes, we identified 5 SNPs associated with DFS (HRrs161041(PPP2R2B)=2.35 (1.68-3.30) in ER/PR+ and HER2-, HRrs1896346(TBX3)=8.19 (3.52-19.08) in ER/PR+ and HER2+, HRrs1278329(ADAM12)=3.96 (2.23-7.02) in ER/PR- and HER2+, HRrs10894375(NTM)=3.10 (2.02-4.74), HRrs10825036(PCDH15)=2.87 (1.90-4.34) in ER/PR- and HER2-) and 3 SNPs associated with OS (HRrs7659008(LYPLA1P2)=0.20 (0.09-0.39) in ER/PR+ and HER2-, HRrs4750561(CDNF)=0.12 (0.05-0.29), and HRrs4807216(SF3A2)=11.51 (4.30-30.81) in ER/PR- and HER2+) in breast cancer with the level of P-value<1×10−5. Conclusion: This study suggests that associations between SNPs and survival were heterogeneous according to the molecular subtype of breast cancer. Furthermore, Additional larger studies are needed to replicate these findings. Citation Format: Nan Song, Ji-Yeob Choi, Hyuna Sung, Keun-Young Yoo, Wonshik Han, Dong-Young Noh, Sei-Hyun Ahn, Daehee Kang. A genome-wide association study of breast cancer survival according to molecular subtype in Korean women. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2550. doi:10.1158/1538-7445.AM2013-2550