Data from Plastin Polymorphisms Predict Gender- and Stage-Specific Colon Cancer Recurrence after Adjuvant Chemotherapy

Abstract

<div>Abstract<p>Tumor recurrence after curative resection remains a major problem in patients with locally advanced colorectal cancer treated with adjuvant chemotherapy. Genetic single-nucleotide polymorphisms (SNP) may serve as useful molecular markers to predict clinical outcomes in these patients and identify targets for future drug development. Recent <i>in vitro</i> and <i>in vivo</i> studies have demonstrated that the plastin genes <i>PLS3</i> and <i>LCP1</i> are overexpressed in colon cancer cells and play an important role in tumor cell invasion, adhesion, and migration. Hence, we hypothesized that functional genetic variations of plastin may have direct effects on the progression and prognosis of locally advanced colorectal cancer. We tested whether functional tagging polymorphisms of <i>PLS3</i> and <i>LCP1</i> predict time to tumor recurrence (TTR) in 732 patients (training set, 234; validation set, 498) with stage II/III colorectal cancer. The <i>PLS3</i> rs11342 and <i>LCP1</i> rs4941543 polymorphisms were associated with a significantly increased risk for recurrence in the training set. <i>PLS3</i> rs6643869 showed a consistent association with TTR in the training and validation set, when stratified by gender and tumor location. Female patients with the <i>PLS3</i> rs6643869 AA genotype had the shortest median TTR compared with those with any G allele in the training set [1.7 vs. 9.4 years; HR, 2.84; 95% confidence interval (CI), 1.32–6.1; <i>P</i> = 0.005] and validation set (3.3 vs. 13.7 years; HR, 2.07; 95% CI, 1.09–3.91; <i>P</i> = 0.021). Our findings suggest that several SNPs of the <i>PLS3</i> and <i>LCP1</i> genes could serve as gender- and/or stage-specific molecular predictors of tumor recurrence in stage II/III patients with colorectal cancer as well as potential therapeutic targets. <i>Mol Cancer Ther; 13(2); 528–39. ©2013 AACR</i>.</p></div>