Purpose: The role of microRNAs (miRNAs) in tumorigenesis has been well established. Genetic variants in the miRNA biogenesis pathway genes may modify cancer development and survival by affecting the miRNA biogenesis. Our aim is to investigate the association of polymorphisms in the miRNA biogenesis pathway genes and malignant peripheral nerve sheath tumor (MPNST) risk among neurofibromatosis type 1 (NF1) patients.
Methods: A case-control study was performed to analyze 53 SNPs in 11 miRNA biogenesis pathway genes in 356 patients (200 patients with NF1 and 156 patients with both NF1 and MPNST) in China. Association analysis was performed in an additive genetic model by logistics regression.
Results: Four SNPs (DDX5 rs1991401, OR=1.79, 95% CI, 1.34-2.38, P=7.90 × 10(-5); DROSHA rs10719, OR=1.64, 95% CI, 1.23-2.20, P=8.76 × 10(-4); AGO2 rs7005286, OR=0.48, 95% CI, 0.32-0.72, P=3.46 × 10(-4); GEMIN4 rs7813, OR=0.50, 95% CI, 0.34-0.72, P=2.65 × 10(-4)) were significantly associated with MPNST risk. A strong gene-dose effect with increased MPNST risk (P for trend<0.001) was observed.
Conclusions: Genetic variants in the miRNA biogenesis pathway genes may modify MPNST risk both individually and jointly.
Keywords: 95% CI; 95% confidence intervals; Genetic variants; MPNST; NF1; OR; malignant peripheral nerve sheath tumors; miRNA; microRNA; neurofibromatosis type 1; odds ratios; pri-miRNA; primary precursors.
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