Department of Obstetrics and Gynecology, Taichung Veterans General Hospital, Institute of Biochemistry and Biotechnology, Chung Shan Medical University, Taichung, Taiwan, ROC.
Clin Chem Lab Med. 2010 Mar;48(3):337-44. doi: 10.1515/CCLM.2010.082.
The goal of our study was to evaluate the influence of genetic polymorphisms of matrix metalloproteinases (MMP)-2, MMP-3 and MMP-7 on susceptibility to endometrial cancer.
In the present study, we enrolled a total of 118 patients with endometrial cancer confirmed by histopathology, and 229 unrelated healthy individuals. Polymorphism for the MMP-2 (rs2285053), MMP-3 (rs3025058) and MMP-7 (rs11568818) genes was genotyped by polymerase chain reaction-restriction enzyme length polymorphism.
The frequencies of MMP-7 -181 G/G and A/G genotypes were found to be significantly higher in cancer patients compared with healthy controls (p = 0.017). Stratification showed that individuals with MMP-7 -181 G allele were at increased risk for endometrial cancer when >50 years of age [odds ratios (OR) = 2.03; 95% confidence interval (CI) 1.21-3.39], endometrioid (OR = 1.80; 95% CI 1.11-2.92), low (stage I-II) (OR = 1.73; 95% CI 1.05-2.83) or high stage (stage III-IV) (OR = 2.69; 95% CI 1.16-6.24). Compared with the A/A genotype, the A/G + G/G genotype modified the risk of developing endometrial carcinoma and significance was detected in patients over 50 years old, and those with endometrioid type and high stage endometrial cancer. However, no significant difference in MMP-2 (-735 C/T) and MMP-3 (6A/5A) genotypes was observed between endometrial carcinoma cases and controls.
This is the first report on the association of MMP-2, MMP-3 and MMP-7 gene polymorphisms in endometrial cancer. Our results suggest that individuals with the MMP-7 -181 G/G and A/G genotype may have an increased risk of developing endometrial cancer.
本研究旨在评估基质金属蛋白酶（MMP）-2、MMP-3 和 MMP-7 的遗传多态性对子宫内膜癌易感性的影响。
本研究共纳入 118 例经组织病理学证实的子宫内膜癌患者和 229 例无关健康个体。采用聚合酶链反应-限制性内切酶长度多态性方法对 MMP-2（rs2285053）、MMP-3（rs3025058）和 MMP-7（rs11568818）基因的多态性进行基因分型。
与健康对照组相比，癌症患者中 MMP-7-181G/G 和 A/G 基因型的频率明显更高（p=0.017）。分层分析显示，MMP-7-181G 等位基因携带者年龄>50 岁时患子宫内膜癌的风险增加[比值比（OR）=2.03；95%置信区间（CI）1.21-3.39]，子宫内膜样（OR=1.80；95%CI 1.11-2.92）、低（I-II 期）（OR=1.73；95%CI 1.05-2.83）或高（III-IV 期）（OR=2.69；95%CI 1.16-6.24）。与 A/A 基因型相比，A/G+G/G 基因型改变了子宫内膜癌的发病风险，且在 50 岁以上患者、子宫内膜样型和高分期子宫内膜癌患者中差异有统计学意义。然而，MMP-2（-735C/T）和 MMP-3（6A/5A）基因型在子宫内膜癌病例与对照组之间无显著差异。
这是首次报道 MMP-2、MMP-3 和 MMP-7 基因多态性与子宫内膜癌的相关性。我们的研究结果表明，MMP-7-181G/G 和 A/G 基因型的个体可能有更高的患子宫内膜癌风险。
