title: Genetic polymorphism of the tissue inhibitor of metalloproteinase-1 is associated with an increased risk of endometrial cancer.
abstract: 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.
  
  
  CONCLUSIONS
  Individuals with TIMP-1_372C/C genotype were at significantly higher risk of endometrial cancer.
authors.affiliation: Department of Obstetrics and Gynecology, Taichung Veterans General Hospital, Taichung, Taiwan.
authors.forename: Yu-Chiao
authors.initials: YC
authors.lastname: Yi
authors.forename: Mu-Kuan
authors.initials: MK
authors.lastname: Chen
authors.forename: Ling-Yun
authors.initials: LY
authors.lastname: Chen
authors.forename: Esther Shih-Chu
authors.initials: ES
authors.lastname: Ho
authors.forename: Tsung-Ho
authors.initials: TH
authors.lastname: Ying
authors.forename: Po-Hui
authors.initials: PH
authors.lastname: Wang
authors.forename: Shun-Fa
authors.initials: SF
authors.lastname: Yang
mesh_terms: D016022:Case-Control Studies; D016889:Endometrial Neoplasms / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics*
chemical_list: D019715:Tissue Inhibitor of Metalloproteinase-1