Genetic Predisposition of Polymorphisms in HMGB1-Related Genes to Breast Cancer Prognosis in Korean Women / 한국유방암학회지
Journal of Breast Cancer
; : 27-34, 2017.
Article
em En
| WPRIM
| ID: wpr-148359
Biblioteca responsável:
WPRO
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.
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Texto completo:
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Base de dados:
WPRIM
Assunto principal:
Polimorfismo Genético
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Prognóstico
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Variação Genética
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Mama
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Neoplasias da Mama
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Modelos de Riscos Proporcionais
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Apoptose
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Intervalo Livre de Doença
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Predisposição Genética para Doença
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Metaloproteinase 2 da Matriz
Tipo de estudo:
Prognostic_studies
Limite:
Female
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Humans
País/Região como assunto:
Asia
Idioma:
En
Revista:
Journal of Breast Cancer
Ano de publicação:
2017
Tipo de documento:
Article