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. 2016 Jun 7;7(23):35015-25.
doi: 10.18632/oncotarget.9014.

Significance of microRNA-related variants in susceptibility to recurrence of oropharyngeal cancer patients after definitive radiotherapy

Xingming Chen  1   2 , Erich M Sturgis  2   3 , Chengyuan Wang  1   4 , Xiaoli Cao  1   5 , Yuncheng Li  1   6 , Qingyi Wei  7 , Guojun Li  2   3
Affiliations

Significance of microRNA-related variants in susceptibility to recurrence of oropharyngeal cancer patients after definitive radiotherapy

Xingming Chen et al. Oncotarget. .

Abstract

Common single nucleotide polymorphisms (SNPs) in miRNAs may affect miRNA functions and their target expression and thus may affect biological activities and cancer etiology as well as prognosis. Thus, we determined whether the 9 SNPs in microRNAs modify the risk of recurrence of squamous cell carcinoma of the oropharynx (SCCOP) in a cohort of 1008 patients. The log-rank test and multivariate Cox models were used to evaluate the associations. We found that the SNPs in the miRNA146, miRNA196, and Gemin3 were associated with a significantly reduced and increased risk of SCCOP recurrence after multivariate adjustment (aHR, 0.6, 95%CI, 0.4-0.9, aHR, 2.1, 95%CI, 1.6-2.8, and aHR, 0.6, 95%CI, 0.5-0.9, respectively). Furthermore, the similar effect of these 3 SNPs on SCCOP recurrence risk was found in HPV-positive SCCOP patients only. However, no significant associations were found for other SNPs. To evaluate the aggregate effects of these SNPs, we performed a combined risk genotype analysis. We found that, compared with the low-risk reference group with less than 4 risk genotypes, the medium-risk group with 4 or 5 risk genotypes exhibited a 1.7-fold (1.2-2.4) increased risk whereas the high-risk group with more than 5 risk genotypes exhibited a 3.0-fold (1.7-4.2) increased risk (Ptrend < 0.001). Such combined effects were particularly pronounced in HPV-positive SCCOP patients. Taken together, this is the first study with a large cohort of SCCOP patients showing that miRNA-related genetic variants may modify risk of SCCOP recurrence individually and jointly. Larger studies are needed to validate these results.

Keywords: HPV; miRNA; oropharyngeal cancer; recurrence; variants.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1A-B
Figure 1A-B. Kaplan-Meier estimates of the cumulative recurrence rates in patients by miRNA-related genotypes (N = 1008)
Figure 2A-B
Figure 2A-B. Kaplan-Meier estimates of the cumulative recurrence rates in HPV-positive SCCOP patients by miRNA-related genotypes (N = 324)
See this image and copyright information in PMC

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