Open AccessThe polymorphisms of mi RNA ‐binding site in MLH 3 and ERCC 1 were linked to the risk of colorectal cancer in a case–control study
Author(s) -
Zhang Qianye,
Zheng Xiao,
Li Xiaoxia,
Sun Deyu,
Xue Ping,
Zhang Guopei,
Xiao Mingyang,
Cai Yuan,
Jin Cuihong,
Yang Jinghua,
Wu Shengwen,
Lu Xiaobo
Publication year - 2018
Publication title -
cancer medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 53
ISSN - 2045-7634
DOI - 10.1002/cam4.1319
Subject(s) - ercc1 , colorectal cancer , genotype , biology , gene , medicine , cancer , genetics , nucleotide excision repair , dna repair
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 MLH 3 rs10862, ERCC 1 rs3212986, ERCC 1 rs735482, ERCC 1 rs2336219, and OGG 1 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 mi RNA can regulate its target gene and the selected SNP s have a valid effect on the target mi RNA . Finally, both of ERCC 1 rs3212986 and MLH 3 rs108621 were shown to be associated with the risk of CRC . Comparing with rs3212986 CC genotype, AA was at a higher risk ( OR = 3.079, 95% CI : 1.192–7.952). For MLH 3 rs108621, comparing with TT genotype, CC and TC were at a higher risk of CRC in male ( OR = 5.171, 95% CI : 1.009–26.494; OR = 1.904, 95% CI : 1.049–3.455). Interestingly, an analysis combining both ERCC 1 rs3212986 and MLH 3 rs108621 also showed an increased risk of CRC . In addition, a dual‐luciferase assay showed that miR‐193a‐3p could regulate MLH 3, and the polymorphism rs108621 could alter the miR‐193a‐3p binding to MLH 3 . Therefore, MLH 3 rs108621 may be associated with the risk of CRC due to the effect of miR‐193a‐3p on MLH 3, which reminded the possibility as potential susceptibility biomarkers to predict the risk of CRC .