title: Genetic Predisposition of Polymorphisms inHMGB1-Related Genes to Breast Cancer Prognosis in Korean Women.
abstract: OBJECTIVE
  The high mobility group box 1 (HMGB1) protein has roles in apoptosis and immune responses by acting as a ligand for receptor for advanced glycation end products (RAGE), Toll-like receptors (TLRs), and triggering receptor expressed on myeloid cells 1. In particular, HMGB1/RAGE is involved in tumor metastasis by inducing matrix metalloproteinase 2 (MMP2) and MMP9 expression. We investigated the associations between genetic variations inHMGB1-related genes and disease-free survival (DFS) and overall survival (OS) in Korean female breast cancer patients.
  
  
  METHODS
  A total of 2,027 patients in the Seoul Breast Cancer Study were included in the analysis. One hundred sixteen single nucleotide polymorphisms (SNPs) were extracted from eight genes. A multivariate Cox proportional hazards model was used to estimate the hazard ratio and 95% confidence interval (CI) of each SNP. The effects of the SNPs on breast cancer prognosis were assessed at cumulative levels with polygenic risk scores.
  
  
  RESULTS
  The SNPs significantly associated with DFS were rs243867 (hazard ratio, 1.26; 95% CI, 1.05-1.50) and rs243842 (hazard ratio, 1.24; 95% CI, 1.03-1.50); both SNPs were inMMP2. The SNPs significantly associated with OS were rs243842 inMMP2(hazard ratio, 1.33; 95% CI 1.03-1.71), rs4145277 inHMGB1(hazard ratio, 1.29; 95% CI, 1.00-1.66), rs7656411 inTLR2(hazard ratio, 0.76; 95% CI, 0.60-0.98), and rs7045953 inTLR4(hazard ratio, 0.50; 95% CI, 0.29-0.84). The polygenic risk score results for the DFS and OS patients showed third tertile hazard ratios of 1.72 (95% CI, 1.27-2.34) and 2.75 (95% CI, 1.79-4.23), respectively, over their first tertile references.
  
  
  CONCLUSIONS
  The results of the present study indicate that genetic polymorphisms inHMGB1-related genes are related to breast cancer prognosis in Korean women.
authors.affiliation: Department of Biological Sciences, KAIST, Daejeon, Korea.; Cancer Research Institute, Seoul National University, Seoul, Korea.
authors.forename: Junsu
authors.initials: J
authors.lastname: Lee
authors.affiliation: Department of Biomedical Sciences, Seoul National University Graduate School, Seoul, Korea.
authors.forename: Jaesung
authors.initials: J
authors.lastname: Choi
authors.affiliation: Division for New Health Technology Assessment, National Evidence-based Healthcare Collaborating Agency, Seoul, Korea.
authors.forename: Seokang
authors.initials: S
authors.lastname: Chung
authors.affiliation: Department of Biomedical Sciences, Seoul National University Graduate School, Seoul, Korea.
authors.forename: JooYong
authors.initials: J
authors.lastname: Park
authors.affiliation: Department of Biomedical Sciences, Seoul National University Graduate School, Seoul, Korea.
authors.forename: Ji-Eun
authors.initials: JE
authors.lastname: Kim
authors.affiliation: Division of Epidemiology and Genetics, National Cancer Institute, Rockville, USA.
authors.forename: Hyuna
authors.initials: H
authors.lastname: Sung
authors.affiliation: Cancer Research Institute, Seoul National University, Seoul, Korea.; Department of Surgery, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Wonshik
authors.initials: W
authors.lastname: Han
authors.affiliation: Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Jong Won
authors.initials: JW
authors.lastname: Lee
authors.affiliation: Cancer Research Institute, Seoul National University, Seoul, Korea.; Department of Biomedical Sciences, Seoul National University Graduate School, Seoul, Korea.; Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Sue K
authors.initials: SK
authors.lastname: Park
authors.affiliation: Division of Cancer Epidemiology and Management, National Cancer Center, Goyang, Korea.
authors.forename: Mi Kyung
authors.initials: MK
authors.lastname: Kim
authors.affiliation: Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Sei-Hyun
authors.initials: SH
authors.lastname: Ahn
authors.affiliation: Cancer Research Institute, Seoul National University, Seoul, Korea.; Department of Surgery, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Dong-Young
authors.initials: DY
authors.lastname: Noh
authors.affiliation: Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Keun-Young
authors.initials: KY
authors.lastname: Yoo
authors.affiliation: Cancer Research Institute, Seoul National University, Seoul, Korea.; Department of Biomedical Sciences, Seoul National University Graduate School, Seoul, Korea.; Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Korea.; Institute of Environmental Medicine, Seoul National University Medical Research Center, Seoul, Korea.
authors.forename: Daehee
authors.initials: D
authors.lastname: Kang
authors.affiliation: Cancer Research Institute, Seoul National University, Seoul, Korea.; Department of Biomedical Sciences, Seoul National University Graduate School, Seoul, Korea.; Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Ji-Yeob
authors.initials: JY
authors.lastname: Choi
keywords: Breast neoplasms; HMGB1 protein; Matrix metalloproteinase 2; Survival