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.
Highlights
Despite the decrease in smoking rate, the incidence of squamous cell carcinoma of the oropharynx (SCCOP) has increased rapidly in recent years because of the increasing infection of human papillomavirus (HPV) [1,2,3,4]
We found that the single nucleotide polymorphisms (SNPs) in the miRNA146, miRNA196, and Gemin3 were associated with a significantly reduced and increased risk of SCCOP recurrence after multivariate adjustment
We found that patients carrying miRNA146rs2910164 GG and Gemin3rs197388 CC genotypes had an approximately 40% significantly lower risk of recurrence than those carrying miRNA146rs2910164 CG+CC and Gemin3rs197388 CA+AA genotypes
Summary
Despite the decrease in smoking rate, the incidence of SCCOP has increased rapidly in recent years because of the increasing infection of human papillomavirus (HPV) [1,2,3,4]. The effects of 9 SNPs on risk of recurrence were assessed among 324 HPV16-positive [HPV16(+)] patients given the key roles of both HPV status and miRNA polymorphisms in SCCOP development and prognosis.
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