Genetic Predisposition of Polymorphisms in HMGB1-Related Genes to Breast Cancer Prognosis in Korean Women.
- Author:
Junsu LEE
1
;
Jaesung CHOI
;
Seokang CHUNG
;
JooYong PARK
;
Ji Eun KIM
;
Hyuna SUNG
;
Wonshik HAN
;
Jong Won LEE
;
Sue K PARK
;
Mi Kyung KIM
;
Sei Hyun AHN
;
Dong Young NOH
;
Keun Young YOO
;
Daehee KANG
;
Ji Yeob CHOI
Author Information
- Publication Type:Original Article
- Keywords: Breast neoplasms; HMGB1 protein; Matrix metalloproteinase 2; Survival
- MeSH: Advanced Glycosylation End Product-Specific Receptor; Apoptosis; Breast Neoplasms*; Breast*; Disease-Free Survival; Female; Genetic Predisposition to Disease*; Genetic Variation; HMGB1 Protein; Humans; Matrix Metalloproteinase 2; Myeloid Cells; Neoplasm Metastasis; Polymorphism, Genetic; Polymorphism, Single Nucleotide; Prognosis*; Proportional Hazards Models; Seoul; Toll-Like Receptors
- From:Journal of Breast Cancer 2017;20(1):27-34
- CountryRepublic of Korea
- Language:English
- Abstract: PURPOSE: 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 in HMGB1-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 in MMP2. The SNPs significantly associated with OS were rs243842 in MMP2 (hazard ratio, 1.33; 95% CI 1.03–1.71), rs4145277 in HMGB1 (hazard ratio, 1.29; 95% CI, 1.00–1.66), rs7656411 in TLR2 (hazard ratio, 0.76; 95% CI, 0.60–0.98), and rs7045953 in TLR4 (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. CONCLUSION: The results of the present study indicate that genetic polymorphisms in HMGB1-related genes are related to breast cancer prognosis in Korean women.
