The Modifying Effect of a Functional Variant at the miRNA Binding Site in E2F1 Gene on Recurrence of Oropharyngeal Cancer Patients with Definitive Radiotherapy

Human papillomavirus (HPV) activates E2F1-driven transcription via the E7-RB-E2F1 pathway. A polymorphism in the 3’ UTR of E2F1 gene may disrupt a binding site for miRNA and may affect its transcription level, thus modifying the susceptibility to radiotherapy and outcomes through this pathway. We evaluated the association of a polymorphism at the 3'UTR miRNA binding site of E2F1 gene (rs3213180) with risk of recurrence of SCCOP in a cohort of 1008 patients. Log-rank test and univariate and multivariable Cox models were used to evaluate the associations. Compared with patients with E2F1-rs3213180 GG homozygous genotype, the patients with E2F1-rs3213180GC + CC variant genotypes had significantly better disease-free survival (log-rank P <.001) and decreased risk of SCCOP recurrence (HR, 0.4, 95% CI, 0.3–0.5) after multivariable adjustment. Furthermore, among patients with HPV16-positive tumors, the patients with E2F1-rs3213180 GC + CC variant genotypes had significantly better disease-free survival rates (log-rank P <.001) and lower recurrence risk than those with E2F1-rs3213180 GG homozygous genotype (HR, 0.2, 95% CI, 0.1–0.4). Our findings suggest that E2F1-rs3213180 polymorphism may modulate the risk of recurrence in SCCOP patients, particularly for patients with HPV16-positive tumors of SCCOP. However, future larger population and functional studies are warranted to validate these results.