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Prediction of breast cancer survival using clinical and genetic markers by tumor subtypes

 Nan Song  ;  Ji-Yeob Choi  ;  Hyuna Sung  ;  Sujee Jeon  ;  Seokang Chung  ;  Sue K. Park  ;  Wonshik Han  ;  Jong Won Lee  ;  Mi Kyung Kim  ;  Ji-Young Lee  ;  Keun-Young Yoo  ;  Bok-Ghee Han  ;  Sei-Hyun Ahn  ;  Dong-Young Noh  ;  Daehee Kang 
 PLoS One, Vol.10(4) : e0122413, 2015 
Journal Title
 PLoS One 
Issue Date
Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/classification ; Breast Neoplasms/genetics ; Breast Neoplasms/pathology* ; Case-Control Studies ; Female ; Genetic Markers* ; Genome-Wide Association Study ; Humans ; Middle Aged ; Prognosis ; Republic of Korea
PURPOSE: To identify the genetic variants associated with breast cancer survival, a genome-wide association study (GWAS) was conducted of Korean breast cancer patients. METHODS: From the Seoul Breast Cancer Study (SEBCS), 3,226 patients with breast cancer (1,732 in the discovery and 1,494 in the replication set) were included in a two-stage GWAS on disease-free survival (DFS) by tumor subtypes based on hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2). The associations of the re-classified combined prognostic markers through recursive partitioning analysis (RPA) of DFS for breast cancer were assessed with the Cox proportional hazard model. The prognostic predictive values of the clinical and genetic models were evaluated by Harrell's C. RESULTS: In the two-stage GWAS stratified by tumor subtypes, rs166870 and rs10825036 were consistently associated with DFS in the HR+ HER2- and HR- HER2- breast cancer subtypes, respectively (Prs166870 = 2.88 × 10(-7) and Prs10825036 = 3.54 × 10(-7) in the combined set). When patients were classified by the RPA in each subtype, genetic factors contributed significantly to differentiating the high risk group associated with DFS inbreast cancer, specifically the HR+ HER2- (P discovery=1.18 × 10(-8) and P replication = 2.08 × 10(-5)) and HR- HRE2- subtypes (P discovery = 2.35 × 10(-4) and P replication = 2.60 × 10(-2)). The inclusion of the SNPs tended to improve the performance of the prognostic models consisting of age, TNM stage and tumor subtypes based on ER, PR, and HER2 status. CONCLUSION: Combined prognostic markers that include clinical and genetic factors by tumor subtypes could improve the prediction of survival in breast cancer.
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1. Journal Papers (연구논문) > 5. Research Institutes (연구소) > Yonsei Cardiovascular Research Institute (심혈관연구소)
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이지영(Lee, Ji Young)
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