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


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.

SUBMITTER: Ting WC 

PROVIDER: S-EPMC3691801 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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

Ting Wen-Chien WC   Chen Lu-Min LM   Pao Jiunn-Bey JB   Yang Ying-Pi YP   You Bang-Jau BJ   Chang Ta-Yuan TY   Lan Yu-Hsuan YH   Lee Hong-Zin HZ   Bao Bo-Ying BY  

International journal of medical sciences 20130615 8


<h4>Background</h4>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.<h4>Methods</h4>We s  ...[more]

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