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

摘要

Human papillomavirus (HPV) activatesE2F1-driven transcription via the E7-RB-E2F1pathway. A polymorphism in the 3’ UTR ofE2F1gene 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 ofE2F1gene (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 withE2F1-rs3213180 GG homozygous genotype, the patients withE2F1-rs3213180GC+CC variant genotypes had significantly better disease-free survival (log-rankP<.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 withE2F1-rs3213180 GC+CC variant genotypes had significantly better disease-free survival rates (log-rankP<.001) and lower recurrence risk than those withE2F1-rs3213180 GG homozygous genotype (HR, 0.2, 95% CI, 0.1–0.4). Our findings suggest thatE2F1-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.