Meta-analysis of associations between polymorphisms in the promoter regions of matrix metalloproteinases and the risk of colorectal cancer.

PURPOSE

Matrix metalloproteinases (MMPs) play important roles in pathogenesis and development of cancer. Recently, lots of studies showed that there were associations between polymorphisms in the promoter regions of MMPs and risk of colorectal cancer; however, the results remained inconclusive. To clarify these associations, we conducted a meta-analysis.

METHODS

We conducted a computerized literature search in the database of PubMed, Embase, ISI Web of Knowledge, and Medline (from January 2000 to July 2010). Overall and subgroup analysis based on the ethnicity of study population was carried out. Odds ratio (OR) and 95% confidence interval (95%CI) were used to evaluate these associations. Statistical analysis was performed with software Review Manager (version 5.0).

RESULTS

There were 12 studies involving five polymorphic sites in four MMP genes. For MMP1 (-1607), 2G polymorphism increased the risk of colorectal cancer under dominant and recessive models (dominant, OR = 1.23, 95%CI 1.01-1.49; recessive, OR = 1.52, 95%CI 1.30-1.77). For MMP3 (-1612), 6A/6A genotype increased this risk under the recessive model (OR = 1.33, 95%CI 1.04-1.70); however, this association was lost under the dominant model. For MMP2 -1306 C>T, MMP3 -1171 5A>6A, and MMP9 -1562 C>T, there was no association between these polymorphisms and the risk of colorectal cancer under the dominant and recessive models.

CONCLUSIONS

Polymorphisms of MMP1 (-1607) and MMP3 (-1612) increased the risk of colorectal cancer; these two polymorphic sites could be used as markers for early diagnosis of colorectal cancer. However, for MMP2 (-1306), MMP3 (-1171), and MMP9 (-1562), further studies with large sample size should be carried out.