A functional polymorphism in the pre-miR-146a gene is associated with risk and prognosis in adult glioma

• Published in: Journal of neuro-oncology 2011-12, Vol.105 (3), p.639-646
• Main Authors: Permuth-Wey, Jennifer, Thompson, Reid C., Burton Nabors, L., Olson, Jeffrey J., Browning, James E., Madden, Melissa H., Ann Chen, Y., Egan, Kathleen M.
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Brain Neoplasms - genetics; Brain Neoplasms - mortality; Brain tumors; Carcinogenesis; Case-Control Studies; Clinical Study – Patient Study; Data processing; Female; Gene polymorphism; Genetic Predisposition to Disease; Genotype; Glioblastoma; Glioma; Glioma - genetics; Glioma - mortality; Guanylate cyclase; Humans; Kaplan-Meier Estimate; Male; Malignancy; Medicine; Medicine & Public Health; MicroRNAs - genetics; Middle Aged; miRNA; Mortality; Neurology; non-coding RNA; Oncogenes; Oncology; Polymorphism, Single Nucleotide; Post-transcription; Prognosis; Proportional Hazards Models; Risk Factors; Single-nucleotide polymorphism; Tumor suppressor genes; Young Adult
• ISSN: 0167-594X; 1573-7373
• DOI: 10.1007/s11060-011-0634-1

MicroRNAs (miRNAs) are non-coding RNAs that function as post-transcriptional regulators of tumor suppressors and oncogenes. Single nucleotide polymorphisms (SNPs) in miRNAs may contribute to carcinogenesis by altering expression of miRNAs and their targets. A G>C polymorphism (rs2910164) in the miR - 146a precursor sequence leads to a functional change associated with the risk for numerous malignancies. A role for this SNP in glioma pathogenesis has not yet been examined. We investigated whether rs2910164 genotypes influence glioma risk and prognosis in a multi-center case–control study comprised of 593 Caucasian glioma cases and 614 community-based controls. Unconditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI) for rs2910164 genotypes according to case status. Cox proportional hazards regression modeling was used to estimate hazards ratios (HR) and 95% CIs according to genotype among glioblastomas, the most lethal glioma subtype. An increased glioma risk was observed among rs2910164 minor allele (C) carriers (per allele OR (95% CI) = 1.22 (1.01–1.46, p trend  = 0.039)). The association was stronger among older subjects carrying at least one copy of the C allele (OR (95% CI) = 1.38 (1.04–1.83, P  = 0.026). Mortality was increased among minor allele carriers (HR (95% CI) = 1.33 (1.03–1.72, P  = 0.029)), with the association largely restricted to females (HR (95% CI) = 2.02 (1.28–3.17, P  = 0.002)). We provide novel data suggesting rs2910164 genotype may contribute to glioma susceptibility and outcome. Future studies are warranted to replicate these findings and characterize mechanisms underlying these associations.