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Background  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.    Methods  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.    Results  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).    Conclusion  Our study indicated that  TIMP-2  rs2277698 was associated with breast cancer susceptibility.

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