International Journal of Medical Sciences

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26 April 2018

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Int J Med Sci 2018; 15(6):580-586. doi:10.7150/ijms.23462

Research Paper

HMGB1 genetic polymorphisms are biomarkers for the development and progression of breast cancer

Bi-Fei Huang1#, Huey-En Tzeng2,3,4#, Po-Chun Chen5, Chao-Qun Wang1, Chen-Ming Su6, Yan Wang7, Gui-Nv Hu8, Yong-Ming Zhao8, Qian Wang1, Chih-Hsin Tang9,5,10✉

1. Department of Pathology, Affiliated Dongyang Hospital of Wenzhou Medical University, Dongyang, Zhejiang, China
2. Taipei Cancer Center, Taipei Medical University, Taipei, Taiwan
3. Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan
4. Department of Internal Medicine, Division of Hematology and Oncology, Taipei Medical University Hospital, Taipei, Taiwan
5. Graduate Institute of Biomedical Science, China Medical University, Taichung, Taiwan
6. Laboratory of Biomedicine, Affiliated Dongyang Hospital of Wenzhou Medical University, Dongyang, Zhejiang, China
7. Department of Medical Oncology, Affiliated Dongyang Hospital of Wenzhou Medical University, Dongyang, Zhejiang, China
8. Department of Surgical Oncology, Affiliated Dongyang Hospital of Wenzhou Medical University, Dongyang, Zhejiang, China
9. Department of Pharmacology, School of Medicine, China Medical University, Taichung, Taiwan
10. Department of Biotechnology, College of Health Science, Asia University, Taichung, Taiwan
# These authors have contributed equally to this work

Abstract

Breast cancer is a major cause of cancer mortality worldwide. High-mobility group box protein 1 (HMGB1) is a ubiquitous nuclear protein found in all mammal eukaryotic cells that participates in tumor progression, migration and metastasis. HMGB1 overexpression has been indicated in breast cancer patients. However, scant information is available regarding the association between HMGB1 single nucleotide polymorphisms (SNPs) and the risk or prognosis of breast cancer. We report on the association between 4 SNPs of the HMGB1 gene (rs1360485, rs1045411, rs2249825 and rs1412125) and breast cancer susceptibility as well as clinical outcomes in 313 patients with breast cancer and in 217 healthy controls. Patients with one G allele in the rs1360485 or rs2249825 domains are likely to progress to T2 tumor and lymph node metastasis. In addition, the presence of one G allele in SNPs rs1360485 or rs2249825 was associated with a higher risk of progressing to T2 tumor and distant metastasis amongst HER2-enriched and triple-negative breast cancer (TNBC) tumors compared with luminal A and luminal B tumors. Furthermore, having one C allele in the rs1412125 domain increased the risk of pathologic grade 3 disease in HER2-enriched and TNBC tumors. Our results indicate that genetic variations in the HMGB1 gene may serve as an important predictor of breast cancer progression and metastasis.

Keywords: HMGB1 polymorphisms, Breast cancer, Single nucleotide polymorphism, Susceptibility

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How to cite this article:
Huang BF, Tzeng HE, Chen PC, Wang CQ, Su CM, Wang Y, Hu GN, Zhao YM, Wang Q, Tang CH. HMGB1 genetic polymorphisms are biomarkers for the development and progression of breast cancer. Int J Med Sci 2018; 15(6):580-586. doi:10.7150/ijms.23462. Available from http://www.medsci.org/v15p0580.htm