Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2017 Apr 1;38(4):432-438.
doi: 10.1093/carcin/bgx019.

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

Lijun Zhu  1   2 , Erich M Sturgis  1   3 , Zhongming Lu  1   4 , Hua Zhang  1   5 , Peng Wei  1   6 , Qingyi Wei  1   7 , Guojun Li  1   3
Affiliations

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

Lijun Zhu et al. Carcinogenesis. .

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.

PubMed Disclaimer

Figures

Figure 1.
Figure 1.
Kaplan–Meier estimates of the cumulative recurrence rates of patients according to miRNA-binding site polymorphisms in DNA repair genes.
Figure 2.
Figure 2.
Kaplan–Meier estimates of the cumulative recurrence rates of patients according to the number of variant genotypes of miRNA-binding site polymorphisms in DNA repair genes.
See this image and copyright information in PMC

References

    1. Parkin D.M., et al. (2005) Global cancer statistics, 2002. CA. Cancer J. Clin., 55, 74–108. - PubMed
    1. Siegel R.L., et al. (2015) Cancer statistics, 2015. CA. Cancer J. Clin., 65, 5–29. - PubMed
    1. Gillison M.L. (2007) Current topics in the epidemiology of oral cavity and oropharyngeal cancers. Head Neck, 29, 779–792. - PubMed
    1. Leemans C.R., et al. (1994) Recurrence at the primary site in head and neck cancer and the significance of neck lymph node metastases as a prognostic factor. Cancer, 73, 187–190. - PubMed
    1. Bagan J.V., et al. (2008) Recent advances in Oral Oncology 2007: epidemiology, aetiopathogenesis, diagnosis and prognostication. Oral Oncol., 44, 103–108. - PubMed

Publication types