Genetic Predisposition of Polymorphisms in HMGB1-Related Genes to Breast Cancer Prognosis in Korean Women.

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.

• Authors: Junsu Lee, 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
• Journal: Journal of breast cancer (J Breast Cancer) Vol. 20 Issue 1 Pg. 27-34 (Mar 2017) ISSN: 1738-6756 [Print] Korea (South)
• PMID: 28382092 (Publication Type: Journal Article)