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. 2013 Jun 15;10(8):1022-7.
doi: 10.7150/ijms.6686. Print 2013.

Genetic polymorphisms of matrix metalloproteinases and clinical outcomes in colorectal cancer patients

Wen-Chien Ting  1 , Lu-Min Chen, Jiunn-Bey Pao, Ying-Pi Yang, Bang-Jau You, Ta-Yuan Chang, Yu-Hsuan Lan, Hong-Zin Lee, Bo-Ying Bao
Affiliations

Genetic polymorphisms of matrix metalloproteinases and clinical outcomes in colorectal cancer patients

Wen-Chien Ting et al. Int J Med Sci. .

Abstract

Background: Colorectal cancer metastasis is a multistep process involving degradation of extracellular matrix components by proteolytic enzymes. Among them, matrix metalloproteinases (MMPs) are the principal degrading enzymes and their expressions/activities are also correlated with survival. Much research has showed the associations between genetic polymorphisms in MMPs and risk of colorectal cancer; however, their prognostic significance has not been well determined.

Methods: We selected and genotyped 4 cancer-associated single nucleotide polymorphisms (SNPs) in a cohort of 282 colorectal cancer patients. The associations of these SNPs with distant metastasis-free survival and overall survival were evaluated by Kaplan-Meier analysis, Cox regression model, and survival tree analysis.

Results: The relative risks of developing distant metastasis after curative surgery were higher in individuals with minor homozygote AA genotype than in those with GG/GA genotypes at MMP2 rs243866 (P = 0.012). Survival tree analysis also identified a higher-order genetic interaction profile consisting of MMP2 rs243866 and MMP2 rs2285053 that was significantly associated with distant metastasis-free survival (P trend = 0.016). After adjusting for possible confounders, the genetic interaction profile remained significant (P trend = 0.050).

Conclusions: These results suggest that genetic variations in the MMP2 might be potential predictors of distant metastasis-free survival after curative surgery.

Keywords: colorectal cancer; matrix metalloproteinases; metastasis; single nucleotide polymorphism; survival..

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interest exists.

Figures

Figure 1
Figure 1
Potential higher order SNP-SNP interactions between MMP2 gene polymorphisms. (A) Survival tree analysis identifies the interactions between MMP2 gene polymorphisms. (B) Kaplan-Meier curves of distant metastasis-free survival based on the survival tree analysis. Numbers in parentheses indicate the number of patients.
See this image and copyright information in PMC

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