Polymorphisms in matrix metalloproteinases 2, 3, and 8 increase recurrence and mortality risk by regulating enzyme activity in gastric adenocarcinoma.

The association of polymorphisms in matrix metalloproteinases (MMPs) with clinical outcomes of gastric adenocarcinoma has not been examined. Ten polymorphisms in MMP1, 2, 3, 7, 8, 9, 12, and 13 were genotyped and investigated, and patients were followed for an average of 58 months. The activities of MMP2, 3, and 8 were measured. Recurrence risk increased in patients with the CC genotype (hazard ratio [HR], 1.85), AA genotype (HR, 2.15), and TT genotype (HR, 2.22) on recurrence free survival (RFS). Co-presence of the unfavorable CC and TT genotypes resulted in an additional increased risk of recurrence (RFS: HR, 4.42; 95% confidence interval [CI], 2.15-9.09; p<0.0001) and risk of death (overall survival ( OS) : HR, 6.59; 95% CI, 3.15-13.19; p<0.0001). Theoretical survival tree analysis revealed that recurrence-free survival significantly varied from 15.5 to 87 months among patients with different polymorphisms in MMP2, 3, and 8. The enzymatic activities of MMP2 and MMP3 increased ( CC: 888.60 vs. CT: 392.00, p <0.0001; AA: 131.10 vs. GG: 107.74, p=0.015), whereas those of MMP8 decreased ( TT: 133.78 vs. CC: 147.54, p=0.011) in gastric cancer tissues. These results suggest that polymorphisms in MMP2, 3, and 8 may increase cancer recurrence and patient death by increasing or decreasing enzyme activity in patients with gastric adenocarcinoma.