Genetic polymorphism of the tissue inhibitor of metalloproteinase-1 is associated with an increased risk of endometrial cancer

Background: Tissue inhibitors of metalloproteinases (TIMPs) are a family of multifunctional proteins known to possess a broad range of biological activities involved in tumorgenesis and mRNA expression of TIMP family members has been shown to be upregulated in numerous cancers and correlates with clinical outcomes. We investigated the association of TIMP-1 and TIMP-2 gene polymorphism with risk of endometrial cancer. Methods: In the present case-control study, we enrolled a total of 118 endometrial cancer patients confirmed by histopathology and 229 unrelated healthy individuals. Polymorphism for TIMP-1 (_372C>T) and TIMP-2 (_418G>C and _303C>T) genes was genotyped by PCR-RFLP. Results: Frequency of TIMP-1_372C/C genotype and 372-C allele differed significantly between patients with endometrial cancer (38.1% and 56.4% respectively) and healthy individuals (22.7% and 44.1% respectively). Individuals with TIMP-1_372 C/C genotype were at higher risk of endometrial cancer (OR = 2.37; 95%CI: 1.33-4.22). Stratification analysis showed that individuals with TIMP-1_372 C/C genotype were at increased risk for endometrioid (OR = 2.46; 95%CI 1.34-4.53) and low stage (stages I-II) endometrial cancer (OR = 3.24; 95%CI 1.22-4.13). However, no significant differences in TIMP-2_418G>C and TIMP-2_303C>T genotypes were observed between endometrial carcinoma cases and controls. Conclusion: Individuals with TIMP-1_372C/C genotype were at significantly higher risk of endometrial cancer. (C) 2009 Elsevier B.V. All rights reserved.