Epidermal growth factor receptor R521K polymorphism shows favorable outcomes in KRAS wild‐type colorectal cancer patients treated with cetuximab‐based chemotherapy

摘要: The R521K polymorphism of epidermal growth factor receptor has attenuated affinity in ligand binding and proto-oncogene induction, which may affect the efficacy cetuximab. We analyzed effect this on outcome 112 patients with KRAS wild-type metastatic colorectal carcinoma treated first-line cetuximab plus FOLFOX-4. associations vascular endothelial (VEGF) expression clinicopathologic characteristics were also examined. results showed that frequencies G/G, G/A, A/A genotypes 32.1% (n = 36), 42.9% (n = 48), 25.0% (n = 28), respectively. A marked decrease VEGF levels (66.7% vs 28.9%, P < 0.01) was observed 521A allele variants (Arg/Lys or Lys/Lys), associated a decreased tumor size (55.6% 31.6%, P = 0.02), good histological differentiation (63.9% 85.5%, P = 0.01), lymphovascular invasion (69.4% 39.5%, P < 0.01), higher response rate to FOLFOX treatment 78.9%, P = 0.01). In addition, longer progression-free period (P = 0.001) overall survival (P = 0.001). By multivariate analysis, identified as an independent prognostic factor. These data suggest receptor, by reducing its activation consequential downregulation target genes, including VEGF, could be key determinant increased cetuximab-based chemotherapy for patients. (Cancer Sci 2012; 103: 791–796)