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.


CONCLUSIONS
Individuals with TIMP-1_372C/C genotype were at significantly higher risk of endometrial cancer.
Yi
Yu-Chiao
YC
Department of Obstetrics and Gynecology, Taichung Veterans General Hospital, Taichung, Taiwan.
Chen
Mu-Kuan
MK
Chen
Ling-Yun
LY
Ho
Esther Shih-Chu
ES
Ying
Tsung-Ho
TH
Wang
Po-Hui
PH
Yang
Shun-Fa
SF
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*
D019715:Tissue Inhibitor of Metalloproteinase-1