MMP-9 -1562 Promoter Polymorphism Associated with Gastric Cancer Risk in Females.

ABSTRACT

Background/Aims: C to T transition at the matrix metalloproteinase-9 (MMP-9) promoter site -1562 abolishes a binding site of a putative transcription repressor protein to the C allelic promoter. The aim of this study is to elucidate the significance of MMP-9 genotypes in clinicopathological manifestations of gastric cancer. Methodology: We conducted a case-control study based on previously stored peripheral blood samples from 263 gastric cancer patients and 354 controls. MMP-9 genotyping was analyzed by PCR-RFLP method. Stratified analysis, logistic regression and Cox proportional hazards analysis were used to evaluate the associations between polymorphisms and gastric cancer development, invasiveness, and survival. Results: There was significant correlation between female patients with MMP-9 -1562 C/T or T/T genotype and higher risk of gastric cancer (OR=2.12, p=0.02). On stratified analysis, only elderly females with T allele had higher risk of gastric cancer (OR=2.64, p=0.04). On Cox proportional hazards analysis, serosal invasion (adjusted HR=3.47, p<0.001) and lymph node metastasis (adjusted HR=2.31, p=0.003), but not MMP-9 polymorphism, were independent prognostic factors for survival. Conclusions: MMP-9 -1562 promoter polymorphism with T allele may be used as a marker to predict gastric cancer development in female subjects, especially in the elderly.