A Common Polymorphism in Pre-microRNA-146a is Associated with Lung Cancer Risk in a Korean Population

Introduction: MicroRNAs (miRs) play important roles in the development and progression of human cancers. MiR-146a down-regulates epidermal growth factor receptor and the nuclear factor-κB regulatory kinase interleukin-1 receptor-associated kinase 1 genes that play important roles in lung carcinogenesis. This study was conducted to evaluate the association between rs2910164C>G, a functional polymorphism in the pre-miR-146a, and lung cancer risk.

Material And Methods: The rs2910164C>G genotypes were determined in 1094 patients with lung cancer and 1100 healthy controls who were frequency matched for age and gender.

Results: The rs2910164 CG or GG genotype was associated with a significantly decreased risk for lung cancer compared to that of the CC genotype (adjusted odds ratio=0.80, 95% confidence interval=0.66-0.96, P=0.02). When subjects were stratified according to smoking exposure (never, light and heavy smokers), the effect of the rs2910164C>G genotype on lung cancer risk was significant only in never smokers (adjusted odds ratio=0.66, 95% confidence interval=0.45-0.96, P=0.03, under a dominant model for the C allele) and decreased as smoking exposure level increased (Ptrend<0.001). In line with this result, the level of miR-146a expression in the tumor tissues was significantly higher in the GG genotype than in the CC or CG genotype only in never-smokers (P=0.02).

Conclusions: These findings suggest that the rs2910164C>G in pre-miR-146a may contribute to genetic susceptibility to lung cancer, and that miR-146a might be involved in lung cancer development.