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The associations between immunity-related genes and breast cancer prognosis in Korean women

 Jaesung Choi  ;  Nan Song  ;  Sohee Han  ;  Seokang Chung  ;  Hyuna Sung  ;  Ji-young Lee  ;  Sunjae Jung  ;  Sue K. Park  ;  Keun-Young Yoo  ;  Wonshik Han  ;  Jong Won Lee  ;  Dong-Young Noh  ;  Daehee Kang  ;  Ji-Yeob Choi 
 PLOS ONE, Vol.9(7) : e103593, 2014 
Journal Title
Issue Date
Breast Neoplasms/genetics* ; Breast Neoplasms/mortality ; Breast Neoplasms/pathology ; Disease-Free Survival ; Female ; Genetic Association Studies ; Genetic Predisposition to Disease ; Humans ; Interleukins/genetics* ; Kaplan-Meier Estimate ; Middle Aged ; Polymorphism, Single Nucleotide ; Prognosis ; Proportional Hazards Models ; Risk ; Seoul
We investigated the role of common genetic variation in immune-related genes on breast cancer disease-free survival (DFS) in Korean women. 107 breast cancer patients of the Seoul Breast Cancer Study (SEBCS) were selected for this study. A total of 2,432 tag single nucleotide polymorphisms (SNPs) in 283 immune-related genes were genotyped with the GoldenGate Oligonucleotide pool assay (OPA). A multivariate Cox-proportional hazard model and polygenic risk score model were used to estimate the effects of SNPs on breast cancer prognosis. Harrell's C index was calculated to estimate the predictive accuracy of polygenic risk score model. Subsequently, an extended gene set enrichment analysis (GSEA-SNP) was conducted to approximate the biological pathway. In addition, to confirm our results with current evidence, previous studies were systematically reviewed. Sixty-two SNPs were statistically significant at p-value less than 0.05. The most significant SNPs were rs1952438 in SOCS4 gene (hazard ratio (HR) = 11.99, 95% CI = 3.62-39.72, P = 4.84E-05), rs2289278 in TSLP gene (HR = 4.25, 95% CI = 2.10-8.62, P = 5.99E-05) and rs2074724 in HGF gene (HR = 4.63, 95% CI = 2.18-9.87, P = 7.04E-05). In the polygenic risk score model, the HR of women in the 3rd tertile was 6.78 (95% CI = 1.48-31.06) compared to patients in the 1st tertile of polygenic risk score. Harrell's C index was 0.813 with total patients and 0.924 in 4-fold cross validation. In the pathway analysis, 18 pathways were significantly associated with breast cancer prognosis (P<0.1). The IL-6R, IL-8, IL-10RB, IL-12A, and IL-12B was associated with the prognosis of cancer in data of both our study and a previous study. Therefore, our results suggest that genetic polymorphisms in immune-related genes have relevance to breast cancer prognosis among Korean women.
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5. Research Institutes (연구소) > Yonsei Cardiovascular Research Institute (심혈관연구소) > 1. Journal Papers
Yonsei Authors
Lee, Ji Young(이지영) ORCID logo https://orcid.org/0000-0002-7784-1401
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