Research Paper Volume 12, Issue 19 pp 19325—19334

TIMP-2 gene rs4789936 polymorphism is associated with increased risk of breast cancer and poor prognosis in Southern Chinese women

Gaoming Liu1,2, , Jiayou Luo1, ,

  • 1 Department of Maternal and Child Health, Xiangya School of Public Health, Central South University, Changsha 410078, Hunan Province, China
  • 2 Department of Women’s Cancer, Hunan Cancer Hospital, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha 410013, Hunan, China

Received: April 30, 2020       Accepted: July 14, 2020       Published: October 7, 2020
How to Cite

Copyright: © 2020 Liu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Tissue inhibitor of metalloproteinase-2 (TIMP-2) is an endogenous inhibitor of matrix metalloproteinase-2, and an important regulator of cancer growth and metastasis. Here, we evaluated the relationship between TIMP-2 gene rs4789936 polymorphism and breast cancer risk and prognosis in Southern Chinese women. Analysis of 480 breast cancer cases and 530 healthy controls revealed that compared to the CC genotype, the TT/CT genotypes increased the risk of breast cancer (CT: odds ratio (OR)=1.46, 95%CI: 1.11-1.92; TT: OR=2.57, 95%CI: 1.76-3.77). Stratified and cross-over analyses indicated that the increased risk of the rs4789936 polymorphism was associated with age, smoking, drinking, and the body mass index. The TT and CT genotypes were more common than the CC genotype in patients with lymph node metastases (TT: OR=2.54, 95%CI: 1.54-4.18; CT: OR=2.10, 95%CI: 1.40-3.15), advanced stage (TT: OR=1.91, 95%CI: 1.17-3.14; CT: OR=1.80, 95%CI: 1.20-2.70), or progesterone receptor positive cancer (TT: OR=2.02, 95%CI: 1.23-3.32). Multivariate cox regression indicated the CT and TT genotypes (HR=4.65, 95%CI: 1.26-17.18, P=0.021; HR=6.62, 95%CI: 1.51-29.11, P=0.012) were associated with poor prognosis in breast cancer patients. Thus, the TIMP-2 gene rs4789936 polymorphism is associated with elevated breast cancer risk and may be an independent prognosis factor in breast cancer patients.


TIMP-2: Tissue inhibitor metalloproteinase-2; OR: odds ratio; CI: confidence interval; MMP: matrix metalloproteinase; BMI: body mass index; PR: progesterone receptor; ER: estrogen receptor; SNP: single nucleotide polymorphism; PCR-RFLP: polymerase chain reaction restriction fragment length polymorphism; HR: hazard ratio; T: thymine (T); C: cytosine.