EGF and EGFR genetic polymorphisms predict prognosis in locally advanced pharyngolaryngeal squamous cell carcinoma patients receiving postoperative concurrent chemoradiotherapy

Abstract

Nai-Wen Su,1 Yi-Shing Leu,2 Jehn-Chuan Lee,2 Chung-Ji Liu,3 Chieh-Yuan Cheng,3 Jiun-Sheng Lin,3 Yu-Jen Chen,4 Chi-Kuan Chen,5 I-Chih Fang,6 Ruey-Kuen Hsieh,1 Yi-Fang Chang1,6 1Division of Medical Oncology and Hematology, Department of Internal Medicine, 2Department of Otorhinolaryngology, 3Department of Oral and Maxillofacial Surgery, 4Department of Radiation Oncology, 5Department of Pathology, 6Good Clinical Research Center, Department of Medical Research, Mackay Memorial Hospital, Taipei, Taiwan Background: Epidermal growth factor (EGF) and its receptor (EGFR) are part of an important signaling pathway that is involved in the pathogenesis of squamous cell carcinoma of the head and neck (SCCHN). We hypothesized that EGF/EGFR genetic polymorphisms might have a prognostic impact on disease-free survival and overall survival (OS) in locally advanced SCCHN. Materials and methods: The patient group included a consecutive cohort of 180 patients with locally advanced SCCHN who underwent postoperative concurrent chemoradiotherapy between 2002 and 2010. DNA from formalin-fixed, paraffin-embedded tumor tissues was genotyped for the single nucleotide polymorphism (SNP) of EGF A61G A>G, EGFR R521K G>A and G-216T. The log-rank test was applied to evaluate the impact of SNPs on the outcomes. Survival was estimated using the Kaplan–Meier statistical method. Results: We demonstrated that EGF/EGFR SNPs might predict prognosis in patients with primary pharyngolaryngeal tumors, but not in those with oral cavity tumors. In pharyngolaryngeal tumor subgroup, EGF61 G/G genotype led to worse 5 year OS rate when compared to G/A or A/A genotypes (13.3% versus 34.3% versus 50.0%, P=0.017). The 5 year OS of patients with EGFR R521K G/G (11.1%) and G/A (15.9%) were lower than the A/A (62.5%) genotype (P=0.054). Patients carrying one or two unfavorable alleles had worse 5 year OS than those without unfavorable allele (not available versus 20% versus 71.4%, P=0.002). Multivariate analysis revealed that the highest risk of death was associated with the coexistence of two unfavorable genotypes (hazard ratio 25.7, 95% confidence interval =3.4–193.4; P=0.002). Conclusion: In this study, we were able to demonstrate that the EGF A61G and EGFR R521K genetic polymorphisms might be important prognostic factors in patients with locally advanced primary pharyngolaryngeal squamous cell carcinoma who underwent postoperative concurrent chemoradiotherapy. Keywords: polymorphisms, EGF A61G, EGFR R521K, head and neck cancer, biomarker