Polymorphism (rs16917496) at the miR-502 Binding Site of the Lysine Methyltransferase 5A (SET8) and its Correlation with Colorectal Cancer in Iranians

نویسندگان

1 Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

2 Department of Internal Medicine, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

3 Department of Internal Medicine, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

4 Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan; Acquired Immunodeficiency Research Center, Isfahan University of Medical Sciences, Isfahan; Gerfa Namayesh Azmayesh (GENAZMA) Science and Research Institute, Isfahan, Iran

5 Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

6 Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

7 Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

8 Department of Pathology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

doi
چکیده

Background: One of the gene expression regulatory mechanisms is mediated by small noncoding RNAs called microRNA (miRNA). They interact with a recognition sequence located mostly in 3'-untranslated regions (3'-UTRs) of mRNAs. Polymorphisms in miRNAs recognition sequences could affect gene expression which in turn may alter disease susceptibility. SET8, a member of the SET domain-containing methyltransferase, acts in a variety of biological processes such as genomic stability. Here, we report correlation of rs16917496 polymorphism, located in the recognition sequence of miR-502 within 3'-UTR of SET8, with colorectal cancer (CRC) in Iranians. Materials and Methods: One hundred and seventy CRC patients and 170 noncancer counterparts were recruited in this case–control study. Genotyping of rs16917496 was performed using polymerase chain reaction-restriction fragment length polymorphism method. Results: There was no significant association of rs16917496 with CRC in population under study (P value for genotype and allele distribution were >0.05). However, stratification analysis based on smoking status revealed that TT+TC genotypes of SET8 rs16917496 are strongly associated with increased risk of CRC (odds ratio: 5.8, 95% confidence interval: 1.37–24.34, P - 0.005) in smoker subgroup. Conclusion: Correlation of rs16917496 T allele with CRC in smokers is emphasizing the importance of individuals' genotype in the recruitment of adverse health hazards of smoking more profoundly for certain people compared to others.