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