Investigation of pre-miR-34a rs35301225 and pri-miR-34b/c rs4938723 polymorphisms in lung cancer

Lung cancer is the most common cancer in the worldwide according to GLOBOCAN 2012. A number of factors play a role in lung cancer etiology. The expression level of some miRNAs in lung cancer has been associated with increased risk of cancer. MicroRNAs (miRNAs) are small (19-25 nucleotides), noncoding RNAs and known as negative gene regulators. miRNAs play an important role in the pathogenesis of human cancers. Because of that, miRNA polymorphisms can be important for carcinogenesis. miR-34 is a family of miRNAs known to have reduced levels of the expression in many human cancers including lung cancer. It functions like tumor suppressors and targets oncogenes like MET, RET and RAB43. In this study we investigated two polymorphisms (rs35301225 C/T, A, rs4938723 T/C) in respectively miR-34a and miR-34b/c. The study population composed of 100 patient with lung cancer and 100 healthy controls. Blood was collected into EDTA-containing tubes and genomic DNA was extracted. Genetic polymorphisms were detected by using polymerase chain reaction- based restriction fragment length polymorphism (PCR- RFLP). We found that miR-34b/c rs4938723 variant heterozygote CT was associated with a significant increase in the risk of lung cancer compared with their wild-type homozygote TT (ρ<0.001). There was no polymorphism in 100 controls but we found heterozygous polymorphism in 42 patients. rs4938723 polymorphism of miR-34b/c is thought to play an important role in the pathogenesis of lung cancer. However, no significant effects were observed in the relation between miR-34a polymorphism rs35301225 and human lung cancer. Keywords: lung cancer, miRNA, miR-34a, miR-34b/c, SNP, polimorphism