ERCC1 codon 118 C→T polymorphism associated with ERCC1 expression and outcome of FOLFOX-4 treatment in Asian patients with metastatic colorectal carcinoma.

ABSTRACT

We analyzed the influence of codon 118 C→T polymorphism of ERCC1 on its protein expression levels, clinicopathological features, and outcome of 168 Chinese patients with metastatic colorectal carcinoma that had been treated with first-line FOLFOX-4 chemotherapy. A high prevalence of C/C genotype was noted (47.6%, n = 80; 168 patients in total). A marked increase of ERCC1 protein expression levels was also noted in patients with C/T or T/T genotypes (70%vs 20%; P < 0.01), which was associated with significantly lower response to FOLFOX-4 (36.4%vs 57.5%; p = 0.01), and shorter progression-free (7 months vs 13 months; P < 0.01) and overall (16 months vs 25 months; P < 0.01) survival times. By multivariate analysis, this polymorphism was also identified as an independent prognostic factor (P = 0.02). These data suggest that Asian populations have a significantly higher prevalence of the C/C genotype in ERCC1 codon 118, which could be a key determinant for good responses to oxaliplatin-based treatment and favorable outcomes.