Dataset Information

MicroRNA-Related Genetic Variants Associated with Survival of Head and Neck Squamous Cell Carcinoma.

ABSTRACT: BACKGROUND:Head and neck squamous cell carcinoma (HNSCC) is commonly diagnosed at an advanced stage, and prognosis for such patients is poor. There remains a gap in our understanding of genetic variants related with HNSCC prognosis. miRNA-related single nucleotide polymorphisms (miR-SNPs) are a class of genetic variants with gene-regulatory potential. METHODS:We used a genome-scale approach and independent patient populations in a two-stage approach to test 40,286 common miR-SNPs for association with HNSCC survival in the discovery population (n = 847), and selected the strongest associations for replication in validation phase cases (n = 1,236). Furthermore, we leveraged miRNA interaction databases and miRNA expression data from The Cancer Genome Atlas, to provide functional insight for the identified and replicated associations. RESULTS:Joint population analyses identified novel miR-SNPs associated with overall survival in oral and laryngeal cancers. rs1816158, located within long noncoding RNA MIR100HG, was associated with overall survival in oral cavity cancer (HR, 1.56; 95% confidence interval (CI), 1.21-2.00). In addition, expression of MIR100HG-embedded miRNA, miR-100, was significantly associated with overall survival in an independent cohort of HNSCC cases (HR, 1.25; 95% CI, 1.06-1.49). A SNP in the 3'UTR of SH3BP4 (rs56161233) that overlaps predicted miRNA-binding sites and is predicted to disrupt several miRNA-mRNA interactions was associated with overall survival of laryngeal cancer (HR, 2.57; 95% CI, 1.71-3.86). CONCLUSIONS:This work reveals novel miR-SNPs associated with HNSCC survival, and utilizes miRNA-mRNA interaction and expression data to provide functional support for these associations. IMPACT:These findings extend our understanding of how genetic variation contributes to HNSCC survival, and may contribute to future prognostic models for improved risk stratification.

SUBMITTER: Wilkins OM

PROVIDER: S-EPMC6286226 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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MicroRNA-Related Genetic Variants Associated with Survival of Head and Neck Squamous Cell Carcinoma.

Wilkins Owen M OM Titus Alexander J AJ Salas Lucas A LA Gui Jiang J Eliot Melissa M Butler Rondi A RA Sturgis Erich M EM Li Guojun G Kelsey Karl T KT Christensen Brock C BC

Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 20180607 1

<h4>Background</h4>Head and neck squamous cell carcinoma (HNSCC) is commonly diagnosed at an advanced stage, and prognosis for such patients is poor. There remains a gap in our understanding of genetic variants related with HNSCC prognosis. miRNA-related single nucleotide polymorphisms (miR-SNPs) are a class of genetic variants with gene-regulatory potential.<h4>Methods</h4>We used a genome-scale approach and independent patient populations in a two-stage approach to test 40,286 common miR-SNPs ...[more]

PMID: 29880533

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Project description:Single nucleotide polymorphisms (SNPs) in microRNAs (miRNAs) may alter the processing, transcription, and expression of miRNAs and, thus, may contribute to cancer development. The authors hypothesized that common polymorphisms in pre-miRNAs are associated individually and (more likely) collectively with the risk of squamous cell carcinoma of the head and neck (SCCHN).The authors genotyped 4 common polymorphisms in pre-miRNAs: Homo sapiens miRNA 146a (hsa-mir-146a) (reference SNP 2910164 [rs2910164]; guanine to cytosine [G?C]), hsa-mir-149 (rs2292832; guanine to thymine [G?T]), hsa-mir-196a2 (rs11614913; C?T), and hsa-mir-499 (rs3746444; adenine to guanine [A?G]) in 1109 patients with SCCHN (cases) and in 1130 cancer-free patients (controls) in a non-Hispanic white population that was frequency-matched by age and sex. Univariate and multivariate logistic regression models were used to calculate crude and adjusted odds ratios (ORs) and 95% confidence intervals (CIs).Of the 4 SNPs that were studied, the hsa-mir-499 AG and GG genotypes were associated with a reduced risk of SCCHN (OR, 0.83; 95% CI, 0.69-0.99). When the 4 SNPs were combined according to putative risk genotype, the number of observed risk genotypes was associated with an increased risk of SCCHN in a dose-response manner with ORs of 1.0, 1.20, and 1.40 for individuals who had 0 or 1 risk genotypes, 2 or 3 risk genotypes, and 4 risk genotypes, respectively (P(trend) = .037). Specifically, the risk was 1.23-fold (95% CI, 0.98-fold to 1.56-fold) for individuals with 2 to 4 risk genotypes and 1.40-fold (95% CI, 1.02-fold to 1.92-fold) for individuals who had 4 risk genotypes compared with individuals who had 0 or 1 risk genotypes. This risk was more pronounced in men and in patients with oropharyngeal cancer.The combined risk genotypes of 4 common SNPs in pre-miRNAs were associated significantly with a moderately increased risk of SCCHN. Larger studies are needed to validate the current findings.

Dataset Information

MicroRNA-Related Genetic Variants Associated with Survival of Head and Neck Squamous Cell Carcinoma.

Publications

MicroRNA-Related Genetic Variants Associated with Survival of Head and Neck Squamous Cell Carcinoma.

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