title: The associations between immunity-related genes and breast cancer prognosis in Korean women.
abstract: 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.
authors: Department of Biomedical Sciences, Seoul National University Graduate School, Seoul, Korea.
authors: Jaesung
authors: J
authors: Choi
authors: Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
authors: Nan
authors: N
authors: Song
authors: Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Korea.
authors: Sohee
authors: S
authors: Han
authors: Department of Biomedical Sciences, Seoul National University Graduate School, Seoul, Korea.
authors: Seokang
authors: S
authors: Chung
authors: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, Umited States of America.
authors: Hyuna
authors: H
authors: Sung
authors: Cardiovascular Research Institute and Cardiovascular Genome Center, Yonsei University Health System, Seoul, Korea.
authors: Ji-young
authors: JY
authors: Lee
authors: Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Korea.
authors: Sunjae
authors: S
authors: Jung
authors: Department of Biomedical Sciences, Seoul National University Graduate School, Seoul, Korea; Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea; Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Korea.
authors: Sue K
authors: SK
authors: Park
authors: Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Korea.
authors: Keun-Young
authors: KY
authors: Yoo
authors: Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea; Department of Surgery, Seoul National University College of Medicine, Seoul, Korea.
authors: Wonshik
authors: W
authors: Han
authors: Department of Surgery, University of Ulsan College of Medicine and ASAN Medical Center, Seoul, Korea.
authors: Jong Won
authors: JW
authors: Lee
authors: Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea; Department of Surgery, Seoul National University College of Medicine, Seoul, Korea.
authors: Dong-Young
authors: DY
authors: Noh
authors: Department of Biomedical Sciences, Seoul National University Graduate School, Seoul, Korea; Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea; Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Korea.
authors: Daehee
authors: D
authors: Kang
authors: Department of Biomedical Sciences, Seoul National University Graduate School, Seoul, Korea; Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
authors: Ji-Yeob
authors: JY
authors: Choi
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D007378:Interleukins / Q000235:genetics*; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D016016:Proportional Hazards Models; D012306:Risk; D066106:Seoul
chemical_list: D007378:Interleukins