Lin Xian-dong, Chen Gang, Li Chao, Zhang Li-yuan, Shi Yi, Zhou Dong-mei, Zheng Xiong-wei
Department of Pathology, Fujian Provincial Cancer Hospital, the Teaching Hospital of Fujian Medical University, Fuzhou 350014, China.
Zhonghua Yu Fang Yi Xue Za Zhi. 2011 Aug;45(8):711-6.
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.
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.
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).
Polymorphism of TIMP2 is significantly related with occurrence and development of GC and maybe acts as a new biomarker of GC in prognosis.
本研究旨在探讨基质金属蛋白酶2（MMP2）-1306C/T、金属蛋白酶组织抑制因子2（TIMP2）2379C/T、TIMP2 303G/A基因多态性与中国福建省胃癌（GC）遗传易感性之间的相关性。
进行病例对照研究。采用基质辅助激光解吸电离飞行时间质谱（MALDI-TOF-MS）法检测479例胃癌患者和469例年龄及性别频率匹配的无癌对照者的MMP2-1306C/T、TIMP2 2379C/T、TIMP2 303G/A基因多态性。采用多因素logistic回归分析评估基因多态性与胃癌易感性之间的相关性。使用似然比检验对MMP2-1306C/T与TIMP2 2379C/T或TIMP2 303G/A之间的相互作用进行检验。
胃癌组中TIMP2 303G/A的GG、AG、AA基因型频率分别为55.9%（267/478）、38.7%（185/478）和5.4%（26/478）；对照组中分别为53.1%（243/458）、36.9%（169/458）和10.0%（46/458），患者组与对照组之间差异有统计学意义（χ² = 7.0，P = 0.03）。与AA基因型相比，GG + AG基因型患者患癌风险显著更高，比值比（OR）为1.94（95%可信区间：1.2 - 3.2）。TIMP2 303G/A的GG + AG和AA基因型频率在肌层组分别为87.5%（70/80）、12.5%（10/80），而在浆膜及以外组分别为96.0%（382/398）、4.0%（16/398），肌层组患者与浆膜及以外组患者之间差异有统计学意义（χ² = 9.32，P = 0.002）。与AA基因型相比，GG + AG基因型患者肿瘤侵袭风险显著更高，OR为3.4（95%可信区间：1.5 - 7.8）。TIMP2 2379C/T的CC + CT、TT基因型频率在无淋巴结转移组分别为93.4%（113/121）、6.6%（8/121），而在有淋巴结转移组分别为98.6%（349/354）、1.4%（5/354），TIMP2 2,379C/T基因型分布在无淋巴结转移组与有淋巴结转移组患者之间差异有统计学意义（χ² = 9.16，P = 0.002）。与TT基因型相比，CC + CT基因型患者淋巴结转移风险显著更高，OR为4.9（95%可信区间：1.6 - 15.3）。MMP2-1306C/T基因型与胃癌的肿瘤大小、组织分化、侵袭、TNM分期及淋巴结转移均无关（χ²（肿瘤大小） = 0.05，P = 0.98；χ²（侵袭深度） = 1.87，P = 0.39；χ²（组织学类型） = 0.55，P = 0.76；χ²（淋巴结转移） = 0.44，P = 0.80；χ²（TNM） = 2.6，P = 0.28）。未观察到两个基因多态性之间有显著的相互作用（χ²值分别为0.98和0.80，P值分别为0.81和0.85）。
TIMP2基因多态性与胃癌的发生发展显著相关，可能作为胃癌预后的一种新的生物标志物。
