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KMID : 1134120170200010027
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Journal of Breast Cancer
2017 Volume.20 No. 1 p.27 ~ p.34
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Genetic Predisposition of Polymorphisms in HMGB1-Related Genes to Breast Cancer Prognosis in Korean Women
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Lee Jun-Su
Choi Jae-Sung
Chung Seo-Kang
Park Joo-Yong
Kim Ji-Eun
Sung Hyun-A
Han Won-Shik
Lee Jong-Won
Park Sue-K.
Kim Mi-Kyung
Ahn Sei-Hyun
Noh Dong-Young
Yoo Keun-Young
Kang Dae-Hee
Choi Ji-Yeob
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Abstract
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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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KEYWORD
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Breast neoplasms, HMGB1 protein, Matrix metalloproteinase 2, Survival
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