Polymorphisms in matrix metalloproteinases 2, 3, and 8 increase recurrence and mortality risk by regulating enzyme activity in gastric adenocarcinoma
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Youdong Lin1, Jinsheng Liu2, Long Jin3 and Yun Jiang4
1Fujian Shengli Clinical Medical College of Fujian Medical University and Department of Clinical Laboratory Medicine, Fujian Provincial Hospital, Fuzhou, Fujian 350001, China
2Department of Gastrointestinal Surgery, Fujian Provincial Hospital, Fuzhou, Fujian 350001, China
3Department of Pathology, Fujian Provincial Hospital, Fuzhou, Fujian 350001, China
4Department of VIP Clinic, Fujian Provincial Hospital, Fuzhou, Fujian 350001, China
Youdong Lin, email: firstname.lastname@example.org
Keywords: matrix metalloproteinases; polymorphisms; enzyme activity; gastric adenocarcinoma; clinical outcomes
Received: September 26, 2016 Accepted: October 29, 2017 Published: November 20, 2017
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 MMP2 rs2285053 CC genotype (hazard ratio [HR], 1.85), MMP3 rs679620 AA genotype (HR, 2.15), and MMP8 rs1940475 TT genotype (HR, 2.22) on recurrence free survival (RFS). Co-presence of the unfavorable MMP2 rs2285053 CC and MMP8 rs1940475 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 (MMP2 rs2285053 CC: 888.60 vs. CT: 392.00, p <0.0001; MMP3 rs679620 AA: 131.10 vs. GG: 107.74, p=0.015), whereas those of MMP8 decreased (MMP8 rs1940475 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.
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