Current Evidence on the Association between Mmp-7 (-181a>G) Polymorphism and Digestive System Cancer Risk

Pan Ke, Zhong De Wu, Hua So

Abstract

The matrix metalloproteinase (MMPs) can degrade various components of the extracellular matrix and its functional genetic polymorphisms may contribute to genetic susceptibility to many cancers. Up to now, the association between MMP-7 (-181A>G) and digestive system cancer risk remain inconclusive. To better understand the role of 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 in homozygote comparison (GG vs. AA, OR=1.21, 95% CI=1.12-1.60) and dominant model (GG/GA vs. AA, OR=1.16, 95% CI=1.03-1.46). In 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 of colorectal cancer and ESCC in homozygote comparison (OR=1.13, 95% CI=1.06-1.26) and heterozygote comparison (OR=1.45, 95% CI=1.11-1.91) respectively. 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 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 population.

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