Association between TIMP-2 gene polymorphism and breast cancer in Han Chinese women

• Published in: BMC cancer Vol. 19; no. 1; pp. 446 - 9
• Main Authors: Wang, Kai, Wang, Guanying, Huang, Shangke, Luo, Anqi, Jing, Xin, Li, Gang, Zhou, Yi, Zhao, Xinhan
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 14.05.2019; BioMed Central; BMC
• Subjects: Age; Alleles; Analysis; Bioinformatics; Breast cancer; Cancer genetics; Cancer prevention; Cancer research; Case-control study; Chromosomes; Computational biology; Deoxyribonuclease; Deoxyribonucleic acid; Development and progression; Disease; Disease susceptibility; DNA; Enzymes; Gene expression; Gene polymorphism; Genes; Genetic aspects; Genetic polymorphisms; Han (Chinese people); Haplotypes; Health aspects; Health risk assessment; Lymphatic system; Medical prognosis; Medical research; Metastasis; Mutation; Peripheral blood; Polymorphism; Population; Regression analysis; Risk factors; Single nucleotide polymorphisms; Single-nucleotide polymorphism; Software; TIMP-2; Tissue inhibitor of metalloproteinase 2; Transcription factors; Women; Womens health; Case-control study; TIMP-2; Breast cancer; Gene polymorphism
• ISSN: 1471-2407; 1471-2407
• DOI: 10.1186/s12885-019-5655-8

TIMP-2 gene plays an important role in the development of breast cancer. The present study was conducted to evaluate whether TIMP-2 gene polymorphisms are associated with breast cancer risk in a Han Chinese cohort. Six single nucleotide polymorphisms (SNPs) within the TIMP-2 gene in 571 breast cancer and 578 healthy control subjects were genotyped through the Agena MassARRAY. Logistic regression analysis was used to assess the influence of TIMP-2 polymorphisms on breast cancer. Functional annotation of TIMP-2 variants and TIMP-2 expression were analyzed by bioinformatics. Bioinformatics analysis found that rs4789936 was likely to affect transcription factor binding, motifs, DNase footprint, and DNase peaks; and TIMP-2 was under-expressed in breast cancer, the risk allele of rs4789936 was associated with increased expression of TIMP-2 in peripheral blood samples. Importantly, individuals carrying TIMP-2 rs2277698 T allele have a 19% lower risk of breast cancer than individuals with allele C, providing protection (OR = 0.81, 95%CI = 0.67-0.99, p = 0.041). In the breast cancer patients with c-erb positive and PR positive, when the CC genotype was used as a reference, individuals carrying the TT genotype increased the risk of breast cancer. Haplotype analysis showed "TCC" was associated with a reduced risk of breast cancer (OR = 0.79, 95%CI = 0.63-0.97, p = 0.028). Our study indicated that TIMP-2 rs2277698 was associated with breast cancer susceptibility.