Department of Colorectal Surgery, China Medical University Hospital, Taichung, Taiwan.
Int J Med Sci. 2013 Jun 15;10(8):1022-7. doi: 10.7150/ijms.6686. Print 2013.
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.
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.
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).
These results suggest that genetic variations in the MMP2 might be potential predictors of distant metastasis-free survival after curative surgery.
结直肠癌转移是一个多步骤的过程，涉及到细胞外基质成分的降解，其中基质金属蛋白酶（MMPs）是主要的降解酶，其表达/活性也与生存相关。大量研究表明 MMPs 中的遗传多态性与结直肠癌的风险之间存在关联；然而，其预后意义尚未得到很好的确定。
我们在 282 例结直肠癌患者的队列中选择并对 4 个与癌症相关的单核苷酸多态性（SNP）进行了基因分型。通过 Kaplan-Meier 分析、Cox 回归模型和生存树分析评估这些 SNP 与无远处转移生存和总生存的相关性。
在接受根治性手术后，MMP2 rs243866 中 AA 纯合子个体发生远处转移的相对风险高于 GG/GA 基因型个体（P = 0.012）。生存树分析还确定了一个由 MMP2 rs243866 和 MMP2 rs2285053 组成的高阶遗传相互作用谱，该谱与无远处转移生存显著相关（P 趋势=0.016）。在调整了可能的混杂因素后，遗传相互作用谱仍然显著（P 趋势=0.050）。
这些结果表明，MMP2 中的遗传变异可能是根治性手术后无远处转移生存的潜在预测因子。
