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

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.

MiR-21 as prognostic biomarker in head and neck squamous cell carcinoma patients undergoing an organ preservation protocol

“…MiRNAs are responsive to various cellular stressors and are key players in many diseases including cancer [ 8 , 9 ]. Studies have shown that miRNAs may affect cancer development and the regulation of the immune/inflammation or cell death responses as well as may be used in early detection, diagnosis and prognosis of different diseases [ 10 ].…”

MiRNA Polymorphisms and Cancer Prognosis: A Systematic Review and Meta-Analysis

“…Single nucleotide polymorphisms of miRNAs have been identified to affect miRNA processing and alter miRNA expression (50). Some researchers have shown that miR-492 rs2289030 G > C was associated with various cancers (50, 62, 67, 86). Lee et al found CRC patients carried CG and GG genotype demonstrated worse RFS when compared with CC genotype.…”

microRNAs deregulation in head and neck squamous cell carcinoma

“…93 The variant A allele of SNV Gemin3 (DDX20) rs197388 was associated with altering the process of the mature miRNAs for translational repression compared to the wild-type T allele, and thus with recurrence of OPSCC. 94 Moreover, miR-146 rs2910164 variant C and miR-196 rs11614913 wild-type C alleles were associated with OPSCC poor prognosis, compared to the wild-type G and variant T alleles, respectively, although the exactly mechanism by which these variants may influence OPSCC prognosis was not clear. 94 The variant alleles of SNVs miR-149 rs2292832 T and miR-499 rs3746444 C were associated with poor prognosis compared to the wild-type A and T alleles, respectively, although the exactly mechanism by which these variants may influence OSCC, HPSCC and LSCC prognosis was not clear.…”

“…94 Moreover, miR-146 rs2910164 variant C and miR-196 rs11614913 wild-type C alleles were associated with OPSCC poor prognosis, compared to the wild-type G and variant T alleles, respectively, although the exactly mechanism by which these variants may influence OPSCC prognosis was not clear. 94 The variant alleles of SNVs miR-149 rs2292832 T and miR-499 rs3746444 C were associated with poor prognosis compared to the wild-type A and T alleles, respectively, although the exactly mechanism by which these variants may influence OSCC, HPSCC and LSCC prognosis was not clear. 95 Also, MIR100HG, a long non-coding RNA from which miR-100 originate, rs1816158 variant C allele was associated with poor prognosis in OSCC, pharyngeal SCC and LSCC, compared to the wild-type A allele, possibly due to the miR-100 expression increasing, associated with tumor invasion and migration.…”

“…The variant A allele of SNV Gemin3 ( DDX20 ) rs197388 was associated with altering the process of the mature miRNAs for translational repression compared to the wild‐type T allele, and thus with recurrence of OPSCC 94 . Moreover, miR‐146 rs2910164 variant C and miR‐196 rs11614913 wild‐type C alleles were associated with OPSCC poor prognosis, compared to the wild‐type G and variant T alleles, respectively, although the exactly mechanism by which these variants may influence OPSCC prognosis was not clear 94 …”