The tissue inhibitors of
metalloproteinases (TIMPs) are a family of multifunctional
proteins which have been shown to be upregulated in various types of
cancers. However, the contribution of TIMPs in
breast cancer is not fully understood, not to mention
triple negative breast cancer (TNBC). This study's aim was to evaluate the contribution of
TIMP-1 rs4898, rs6609533, and rs2070584 genotypes to the risk of
breast cancer, especially the subtype of TNBC. The contributions of these
TIMP-1 genotypes to
cancer risk were examined among 1232
breast cancer patients and 1232 healthy controls, and several clinicopathologic factors were also analyzed. The results showed that the percentages of CC, CT, and TT of
TIMP-1 rs4898 were differentially distributed at 28.5%, 33.1% and 38.4% in the
breast cancer patient group and 34.5%, 41.0% and 24.5% in the control group, respectively (P for trend = 7.99*10(-13)). It was also found that the CC genotype carriers were of increased risk for
breast cancer (odds ratio = 1.90, 95% confidence interval = 1.55-2.33, P = 0.0001) than the TT genotype carriers. In addition, we analyzed the allelic frequency distributions of all three TIMP-1s, and the results showed that the C allele of
TIMP-1 rs4898 contributes to an increase in
breast cancer susceptibility (P = 2.41*10(-12)). On the other hand, there was no difference found in the distribution of genotypic or allelic frequencies among the patients and the controls for
TIMP-1 rs6609533 and rs2070584. Thus, it is our conclusion that the CC genotype of
TIMP-1 rs4898 compared to the TT wild-type genotype may increase the risk for
breast cancer, especially TNBC in Taiwan, and may serve as an early detective and predictive marker.