TY - JOUR
T1 - MicroRNA-related genetic variants associated with survival of head and neck squamous cell carcinoma
AU - Wilkins, Owen M.
AU - Titus, Alexander J.
AU - Salas, Lucas A.
AU - Gui, Jiang
AU - Eliot, Melissa
AU - Butler, Rondi A.
AU - Sturgis, Erich M.
AU - Li, Guojun
AU - Kelsey, Karl T.
AU - Christensen, Brock C.
N1 - Publisher Copyright:
© 2018 American Association for Cancer Research.
PY - 2019/1
Y1 - 2019/1
N2 - 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.
AB - 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.
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U2 - 10.1158/1055-9965.EPI-18-0002
DO - 10.1158/1055-9965.EPI-18-0002
M3 - Article
C2 - 29880533
AN - SCOPUS:85060799426
SN - 1055-9965
VL - 28
SP - 127
EP - 136
JO - Cancer Epidemiology Biomarkers and Prevention
JF - Cancer Epidemiology Biomarkers and Prevention
IS - 1
ER -