The miR-196a SNP Rs11614913 but not the miR-499 rs37464444 SNP is a Risk Factor for Non-small Cell Lung Cancer in an Iranian Population

Document Type : Original Article

Authors

1 Department of Immunology and Laboratory Sciences, School of Allied Medical sciences, Dezful University of Medical Sciences, Dezful, Iran

2 Clinical Tuberculosis and Epidemiology Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran

3 Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran,

4 Airways Section, National Heart and Lung Institute, Imperial College London, London, United Kingdom

5 Molecular Medicine Department, Institute of Medical Biotechnology, National Institute of Genetic Engineering and Biotechnology, Tehran, Iran

6 Chronic Respiratory Diseases Research Center, NRITLD, Shahid Beheshti University of Medical Sciences, Tehran, Iran

7 Department of Epidemiology and Reproductive Health, Reproductive Epidemiology Research Center, Royan Institute for Reproductive Biomedicine, Tehran, Iran

8 Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran

9 Chronic Respiratory Diseases Research Center, NRITLD, Shahid Beheshti University of Medical Sciences, Tehran, Iran,

Abstract

Background: Globally, lung cancer represents a major cause of cancer-related deaths. The regulation of gene expression is modulated by small noncoding RNAs called miRNAs that can act as both tumor suppressors and oncogenes. The maturation, expression and binding to target mRNAs is affected by single nucleotide polymorphisms (SNPs) in miRNA genomic regions thereby contributing to cancer susceptibility. SNPs Rs11614913 in miR196a and Rs3746444 in miR-499 are implicated in the development of cancers such as non-small cell lung cancer (NSCLC) in non-Arabic subjects.
Materials and Methods: A small cohort of 204 participants including 104 lung cancer patients and 100 non-cancer controls subjects were enrolled into the study. The allele frequencies were determined by Polymerase Chain Reaction–Restriction Fragment Length Polymorphism (PCR-RFLP) and their correlation with lung cancer risk was determined.
Results: The miR-196a rs11614913 polymorphism increased the risk of NSCLC (CC vs. TT+TC: OR= 2.26, 95%CI= 1.28 – 3.98, P= 0.0046) in a dominant genetic model. No statistically significant association was found between the miR-499 rs37464444 polymorphism and NSCLC.
Conclusion: The rs11614913 polymorphism in miR-196a, but not the miR-499 rs37464444 polymorphism, increased the risk of NSCLC. Further studies with larger sample sizes in correlation with functional outcomes at the cellular level should be undertaken.

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