The correlation between polymorphisms of matrix metalloproteinase-2 and -9 genes and colorectal cancer of Chinese patients / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate whether the polymorphisms of matrix metalloproteinase-2 (MMP-2) and -9 (MMP-9) promoters contribute to the development and progression of colorectal cancer in Chinese population.</p><p><b>METHODS</b>the PCR-based denaturing high-performance liquid chromatography or PCR-restriction fragment length polymorphism technique respectively was applied to analyze the MMP-2 -1306C/T and MMP-9 -1562C/T polymorphisms in normal group (126 individuals) and colorectal cancer group (126 cases). Genotype frequencies were compared between patients and matched controls, and the association of genotypes with clinical-pathological parameters was studied.</p><p><b>RESULTS</b>The frequency of the CC genotype in the MMP-2 gene polymorphism was significantly increased in colorectal cancer patients when compared with controls (P<0.05), and individuals with the CC genotype had an increased risk of developing colorectal cancer compared to those with CT+TT genotypes (OR: 1.959; 95%CI: 1.055-3.637). Significant correlation was found between the depth of tumor invasion and MMP-2 -1306C/T polymorphism in colorectal cancer patients. However, the genotype frequencies of MMP-9 -1562C/T in colorectal cancer patients were similar to those in control subjects.</p><p><b>CONCLUSION</b>Our results indicate that MMP-2 -1306 C/T polymorphism may be associated with genetic susceptibility to colorectal cancer and the invasive capability of colorectal cancer in Chinese patients. And it is easier for the CC genotype cancer to invade through bowel wall.</p>

IGFBP7 plays a potential tumor suppressor role against colorectal carcinogenesis with its expression associated with DNA hypomethylation of exon 1 / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Insulin-like growth factor binding-protein-7 (IGFBP7) was obtained from our previous colonic adenocarcinoma (CRC) and normal mucosa suppression subtraction hybridization (SSH) cDNA libraries. By RT-PCR and immunohistochemistry, we found that IGFBP7 was overexpressed in CRC tissue compared to normal tissue. However, our in vitro experiments performed in 10 CRC cell lines showed that IGFBP7 expressed only in SW480 and Caco2 cell lines, which implied an underlying reversible regulatory mechanism. Using methylation-specific PCR (MSP) and bisulfite sodium PCR (BSP), we found that its expression was associated with DNA hypomethylation of exon1. This was further supported by the in vitro study which showed restored IGFBP7 expression after demethylation agent 5-aza-2'-deoxycytidine treatment. Correlation analysis between IGFBP7 expression and prognosis indicated that overexpression of IGFBP7 in CRC tissue correlated with favourable survival. Investigation of the functional role of IGFBP7 through transfection studies showed that IGFBP7 protein could inhibit growth rate, decrease colony formation activity, and induce apoptosis in RKO and SW620 cells, suggesting it a potential tumor suppressor protein in colorectal carcinogenesis. In conclusion, our study clearly demonstrated that IGFBP7 plays a potential tumor suppressor role against colorectal carcinogenesis and its expression is associated with DNA hypomethylation of exon 1.