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.
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.
Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Unit 1445, 1515 Holcombe Boulevard, Houston, TX 77030-4009, USA.|Department of Oral and Maxillofacial Surgery, Guangdong General Hospital & Guangdong Academy of Medical Sciences, Guangzhou 510515, China.
Lijun
L
Zhu
Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Unit 1445, 1515 Holcombe Boulevard, Houston, TX 77030-4009, USA.|Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Erich M
EM
Sturgis
Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Unit 1445, 1515 Holcombe Boulevard, Houston, TX 77030-4009, USA.|Department of Otorhinolaryngology Head and Neck, Guangdong General Hospital and Guangdong Academy of Medical Sciences, Guangzhou, Guangdong 510080, China.
Zhongming
Z
Lu
Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Unit 1445, 1515 Holcombe Boulevard, Houston, TX 77030-4009, USA.|Department of Otorhinolaryngology-Head & Neck Surgery, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, Shandong Province, 264000, China.
Hua
H
Zhang
Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Unit 1445, 1515 Holcombe Boulevard, Houston, TX 77030-4009, USA.|Department of Biostatistics, The University of Texas MD Anderson Cancer Center, 1400 Pressler St, FCT4.6044, Houston, TX 77030, USA and.
Peng
P
Wei
Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Unit 1445, 1515 Holcombe Boulevard, Houston, TX 77030-4009, USA.|Duke Cancer Institute, Duke University Medical Center, Durham, NC 27710, USA.
Qingyi
Q
Wei
Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Unit 1445, 1515 Holcombe Boulevard, Houston, TX 77030-4009, USA.|Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Guojun
G
Li
D001665:Binding Sites / Q000235:genetics*; D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D059248:Chemoradiotherapy / Q000379:methods; D053903:DNA Breaks, Double-Stranded; D004260:DNA Repair / Q000235:genetics*; D018572:Disease-Free Survival; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012306:Risk
D035683:MicroRNAs