Department of Biochemistry, College of Medicine, Kirkuk University
Introduction: Colorectal cancer (CRC) is the 3rd common malignant disease. Prediction of its risk depending on the individuals' genetic makeup is an essential step for screening and personalized medicine. Different studies implicated MicroRNAs (miRNAs) as potential predictors for CRC risk and prognosis with different findings in various demographic settings. To the present knowledge, no similar work was conducted, so far, to study these relations in our community.
Aim: To determine the prevalence of single nucleotide polymorphisms (SNPs) in genes coding for the miRNAs: mir-146a, mir-423 and mir-196a2 in patients with sporadic CRC. The association of these SNPs with increased CRC risk or advanced tumor stage or grade at diagnosis was also explored.
Materials and Methods: In this case-control study, we enrolled 150 patient subjects with sporadic CRC and 140 sex and age matched cancer free control subjects. Genomic DNA was extracted from venous blood samples and screened for the presence of SNPs in mir146, mir-423 and mir-1962a genes using High Resolution Melting Analysis (HRMA) method, and then results were confirmed by direct sequencing. The SPSS statistical software (version 17) was used to test for the association between the presence of the SNP and the risk of CRC, its stage and grade.
Results: The frequency of the CG genotype of mir-1946a was significantly higher (P < 0.01) in the patient subjects (44%) compared to the control ones (30.7%). This genotype was associated with increased risk of CRC (OR= 1.741, 95 % CI= 1.050 -2.886, P=0.031), late stage cancer (III and V of TNM system, OR=3.562, 95%CI= 1.578-8.039, P=0.002) and poor tumour differentiation (OR=5.267, 95%CI= 1.105- 25.109, P=0.037). Individuals carrying CC genotype showed increased CRC risk compared to the common GG genotype (control: 10%, patients: 15.3%, OR= 2.235, 95 % CI= 1.064- 4.694, P=0.004). Additionally it was associated with late stage tumor (OR= 8.522, 95 % CI= 2.899- 25.049, P= 0.0001) but not tumor grade (OR= 2.950, 95 % CI= 0.389-22.339, P= 0.295). None of the genotypes of mir-423 and mir-196a2 showed any association with neither increased risk of CRC nor late stage or poor differentiation.
Conclusion: Various SNPs of miRNAs showed different correlations with CRC and its pathological characteristics which reflect a complex interaction between the genes and the cellular milieu- that is influenced by the demographic qualities of the studied population. Mir-146 can represent a potential target for screening of CRC and a prognostic marker. Further evaluation in a large scale studies will give a better insight on the effects of SNPs on CRC risk and prognosis.