The polymorphisms of miRNA‐binding site in MLH3 and ERCC1 were linked to the risk of colorectal cancer in a case–control study

摘要

Colorectal cancer (CRC), as a malignant tumor of lower digestive tract, has been found to have an increasing morbidity and mortality in China. It was particularly important to find some earlier biomarkers to predict the risk and prognosis. In this study, several polymorphisms on 3′UTR of three DNA repair genes including MLH3 rs10862, ERCC1 rs3212986, ERCC1 rs735482, ERCC1 rs2336219, and OGG1 rs1052133 were chosen by bioinformatics exploration, and then, a case–control study of 200 CRC cases and controls was performed. Furthermore, a dual‐luciferase assay was also carried out to certify whether the candidate miRNA can regulate its target gene and the selected SNPs have a valid effect on the target miRNA. Finally, both of ERCC1 rs3212986 and MLH3 rs108621 were shown to be associated with the risk of CRC. Comparing with rs3212986 CC genotype, style="fixed-case">AA was at a higher risk ( style="fixed-case">OR = 3.079, 95% style="fixed-case">CI: 1.192–7.952). For style="fixed-case">MLH3 rs108621, comparing with style="fixed-case">TT genotype, style="fixed-case">CC and style="fixed-case">TC were at a higher risk of style="fixed-case">CRC in male ( style="fixed-case">OR = 5.171, 95% style="fixed-case">CI: 1.009–26.494; style="fixed-case">OR = 1.904, 95% style="fixed-case">CI: 1.049–3.455). Interestingly, an analysis combining both style="fixed-case">ERCC1 rs3212986 and style="fixed-case">MLH3 rs108621 also showed an increased risk of style="fixed-case">CRC. In addition, a dual‐luciferase assay showed that miR‐193a‐3p could regulate style="fixed-case">MLH3, and the polymorphism rs108621 could alter the miR‐193a‐3p binding to style="fixed-case">MLH3. Therefore, style="fixed-case">MLH3 rs108621 may be associated with the risk of style="fixed-case">CRC due to the effect of miR‐193a‐3p on style="fixed-case">MLH3, which reminded the possibility as potential susceptibility biomarkers to predict the risk of style="fixed-case">CRC.