Dataset Information

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.

SUBMITTER: Lee J

PROVIDER: S-EPMC5378577 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature

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

Lee Junsu J Choi Jaesung J Chung Seokang S Park JooYong J Kim Ji-Eun JE Sung Hyuna H Han Wonshik W Lee Jong Won JW Park Sue K SK Kim Mi Kyung MK Ahn Sei-Hyun SH Noh Dong-Young DY Yoo Keun-Young KY Kang Daehee D Choi Ji-Yeob JY

Journal of breast cancer 20170324 1

<h4>Purpose</h4>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 <i>HMGB1</i>-related genes and disease-free s ...[more]

PMID: 28382092

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Project description:Prostate cancer (PCa) is the most commonly diagnosed male malignancy and the second biggest cause of cancer death in men of the Western world. Higher incidences of PCa occur in men from North America, Oceania and Western countries, whereas men from Asia and North Africa have a much lower PCa incidence rate. Investigations into this population disparity of PCa incidence, in order to identify potential preventive factors or targets for the therapeutic intervention of PCa, have found differences in both environmental and genetic variations between these populations. Environmental variations include both diet and lifestyle, which vary widely between populations. Evidence that diet comes into play has been shown by men who immigrate from Eastern to Western countries. PCa incidence in these men is higher than men in their native countries. However the number of immigrants developing PCa still doesn't match native black/white men, therefore genetic factors also contribute to PCa risk, which are supported by familial studies. There are a number of genetic polymorphisms that are differentially presented between Western and Eastern men, which are potentially associated with PCa incidence. Androgen and its receptor (AR) play a major role in PCa development and progression. In this study, we focus on genes involved in androgen biosynthesis and metabolism, as well as those associated with AR pathway, whose polymorphisms affect androgen level and biological or physiological functions of androgen. While many of the genetic polymorphisms in this androgen/AR system showed different frequencies between populations, contradictory evidences exist for most of these genes investigated individually as to the true contribution to PCa risk. More accurate measurements of androgen activity within the prostate are required and further studies need to include more African and Asian subjects. As many of these genetic polymorphisms may contribute to different steps in the same biological/physiological function of androgen and AR pathway, an integrated analysis considering the combined effect of all the genetic polymorphisms may be necessary to assess their contribution to PCa initiation and progression.

Dataset Information

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

Publications

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

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