Objective: This study was to explore the correlations between genetic variants in MMP2-1306C/T, TIMP2 2379C/T, TIMP2 303G/A and the genetic susceptibility to gastric carcinoma (GC) in Fujian province, China.
Methods: A case-control study was conducted. Polymorphisms of MMP2-1306C/T, TIMP2 2379C/T, TIMP2 303G/A in 479 gastric carcinoma patients and 469 cancer-free controls, frequency-matched by age and sex, were determined by Matrix-Assisted Laser Desorption/Ionization Time of Flight Mass Spectrometry (MALDI-TOF-MS). Multivariate logistic regression analysis was used to evaluate the correlations between the polymorphisms with the susceptibility to gastric cancer. Tests for an interaction between the MMP2-1306C/T and TIMP2 2379C/T or TIMP2 303G/A were performed using the likelihood ratio test.
Results: The frequencies of GG, AG, AA of TIMP2 303G/A in gastric cancer group were 55.9% (267/478), 38.7% (185/478) and 5.4% (26/478); and those in control group were 53.1% (243/458), 36.9% (169/458) and 10.0% (46/458), which showed a significant difference between the patient and control groups (χ(2) = 7.0, P = 0.03). As compared with AA genotype, patients with GG + AG had a significantly higher risk of the cancer with OR of 1.94 (95%CI: 1.2 - 3.2). The frequencies of GG + AG and AA of TIMP2 303G/A in the muscle group were 87.5% (70/80), 12.5% (10/80), however, those in the serosa and beyond group were 96.0% (382/398), 4.0% (16/398), respectively, which showed a significant difference between the patient in muscle group and the serosa and beyond group (χ(2) = 9.32, P = 0.002). As compared with AA genotype, patients with GG + AG had a significantly higher risk in tumor invasion with OR of 3.4 (95%CI: 1.5 - 7.8). The frequencies of CC + CT, TT of TIMP2 2379C/T in the lymphoma node non-metastasis group were 93.4% (113/121), and 6.6% (8/121), but those in the lymphoma node metastasis group were 98.6% (349/354) and 1.4% (5/354), respectively, which showed a significant difference between the patient in the lymphoma node non-metastasis group and in the lymphoma node metastasis group in genotype distributions of TIMP2 2379C/T) χ(2) = 9.16, P = 0.002). As compared with TT genotype, patients with CC + CT had a significantly higher risk in lymph node metastasis with OR of 4.9 (95%CI: 1.6 - 15.3). MMP2-1306C/T genotype was not associated with tumor size, tissue differentiation, invasion, TNM nor lymph node metastasis of gastric carcinoma (χ(2)(tumor size) = 0.05, P = 0.98; χ(2)(depth of invasion) = 1.87, P = 0.39; χ(2)(histological type) = 0.55, P = 0.76; χ(2)(LN metastasis) = 0.44, P = 0.80; χ(2)(TNM) = 2.6, P = 0.28). There was no significant interaction between the polymorphisms of the two genes observed (χ(2) values were 0.98 and 0.80, P values were 0.81 and 0.85).
Conclusion: Polymorphism of TIMP2 is significantly related with occurrence and development of GC and maybe acts as a new biomarker of GC in prognosis.