Association between miRNA-binding site polymorphisms in double-strand break repair genes and risk of recurrence in patients with squamous cell carcinomas of the non-oropharynx

Abstract

Genetic polymorphisms at miRNA-binding sites may affect miRNA-mediated gene regulation. Thus, miRNA-binding site polymorphisms in double-strand break (DSB) repair genes may affect DNA repair capacity, which in turn could affect cancer prognosis. To determine whether miRNA-binding site polymorphisms in DSB repair genes are associated with the risk of recurrence of squamous cell carcinoma of the non-oropharynx (SCCNOP), we used a log-rank test and multivariable Cox models to evaluate the associations between miRNA-binding site polymorphisms in DSB repair genes and SCCNOP recurrence. Compared with patients without common homozygous genotypes, patients with the variant genotypes of ATM rs227091, LIG3 rs4796030, and RAD51 rs7180135 had significantly better disease-free survival (DFS) (log-rank P = 0.046, 0.002, and 0.041, respectively) and lower risk of disease recurrence [HR (95% CI) = 0.7 (0.6-0.9), 0.6 (0.5-0.9), and 0.7 (0.6-0.9), respectively]. Furthermore, patients with the variant genotypes of these 3 polymorphisms had significantly lower recurrence risk than those without common homozygous genotypes did [HR = 0.3 (95% CI = 0.2-0.7)]. Among patients who received chemoradiation, those with the individual or combined variant genotypes of the three polymorphisms had a significantly lower risk of disease recurrence than those with the individual or combined common homozygous genotypes did. The individual or combined variant genotypes of the ATM rs227091, LIG3 rs4796030, and RAD51 rs7180135 polymorphisms significantly modify the risk of SCCNOP recurrence, particularly for patients treated with chemoradiation. Future prospective studies with larger sample sizes are warranted to validate these findings to enable more effective personalized treatment for SCCNOP patients.