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 in vitro and in vivo studies have demonstrated that the
plastin genes PLS3 and LCP1 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 PLS3 and LCP1 predict time to
tumor recurrence (TTR) in 732 patients (training set, 234; validation set, 498) with stage II/III
colorectal cancer. The PLS3 rs11342 and LCP1 rs4941543 polymorphisms were associated with a significantly increased risk for recurrence in the training set. PLS3 rs6643869 showed a consistent association with TTR in the training and validation set, when stratified by gender and
tumor location. Female patients with the PLS3 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; P = 0.005] and validation set (3.3 vs. 13.7 years; HR, 2.07; 95% CI, 1.09-3.91; P = 0.021). Our findings suggest that several SNPs of the PLS3 and LCP1 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.