Current evidence on associations between the MMP-7 (-181A>G) polymorphism and digestive system cancer risk

Matrix metalloproteinases (MMPs) degrade various components of the extracellular matrix and functional polymorphisms in encoding genes may contribute to genetic susceptibility to many cancers. Up to now, associations between MMP-7 (-181A>G) and digestive system cancer risk have remained inconclusive. To better understand the role of the MMP-7 (-181A>G) genotype in digestive cancer development, we conducted this comprehensive meta-analysis encompassing 3,518 cases and 4,596 controls. Overall, the MMP-7 (-181A>G) polymorphism was associated 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, this polymorphism 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 esophageal SCC 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-based studies (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 the source 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), and dominant 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.