title: A functional polymorphism in the pre-miR-146a gene is associated with risk and prognosis in adult glioma.
abstract: 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.
authors: Department of Cancer Epidemiology, Division of Population Sciences, H. Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Drive, MRC-CANCONT, Tampa, FL 33612-9416, USA.
authors: Jennifer
authors: J
authors: Permuth-Wey
authors: Reid C
authors: RC
authors: Thompson
authors: L
authors: L
authors: Burton Nabors
authors: Jeffrey J
authors: JJ
authors: Olson
authors: James E
authors: JE
authors: Browning
authors: Melissa H
authors: MH
authors: Madden
authors: Y
authors: Y
authors: Ann Chen
authors: Kathleen M
authors: KM
authors: Egan
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001932:Brain Neoplasms / Q000235:genetics* / Q000401:mortality*; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005910:Glioma / Q000235:genetics* / Q000401:mortality*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D016016:Proportional Hazards Models; D012307:Risk Factors; D055815:Young Adult
chemical_list: C542542:MIRN146 microRNA, human; D035683:MicroRNAs