Current Evidence on Associations Between the MMP-7 (-181A>G) Polymorphism and Digestive System Cancer Risk

Abstract

Matrix metalloproteinases (MMPs) degrade various components of the extracellular matrix and functionalpolymorphisms in encoding genes may contribute to genetic susceptibility to many cancers. Up to now, associationsbetween MMP-7 (-181A>G) and digestive system cancer risk have remained inconclusive. To better understandthe role of the MMP-7 (-181A>G) genotype in digestive cancer development, we conducted this comprehensivemeta-analysis encompassing 3,518 cases and 4,596 controls. Overall, the MMP-7 (-181A>G) polymorphism wasassociated with higher digestive system cancer risk on homozygote comparison (GG vs. AA, OR=1.21, 95% CI =1.12-1.60) and in a dominant model (GG/GA vs. AA, OR=1.16, 95% CI =1.03-1.46). On subgroup analysis, thispolymorphism was significantly linked to higher risks for gastric cancer (GG vs. AA, OR=1.22, 95% CI = 1.02-1.46; GA vs. AA, OR=1.82, 95% CI =1.16-2.87; GG/GA vs. AA, OR=1.13, 95% CI =1.01-1.27; GG vs. GA/AA,OR= 1.25, 95% CI = 1.06-2.39. We also observed increased susceptibility to colorectal cancer and esophagealSCC in both homozygote (OR = 1.13, 95% CI = 1.06-1.26) and heterozygote comparisons (OR = 1.45, 95% CI= 1.11-1.91). In the stratified analysis by controls, significant effects were only observed in population-basedstudies (GA vs. AA, OR=1.16, 95% CI=1.08-1.50; GA/AA vs. GG, OR=1.10, 95% CI=1.01-1.72). According to thesource of ethnicity, a significantly increased risk was found among Asian populations in the homozygote model(GG vs. AA, OR=1.40, 95% CI=1.12–1.69), heterozygote model (GA vs. AA, OR=1.26, 95% CI=1.02–1.51), anddominant model (GG/GA vs. AA, OR=1.18, 95% CI=1.08–1.55). Our findings suggest that the MMP-7 (-181A>G)polymorphism may be a risk factor for digestive system cancer, especially among Asian populations.