Association of aNew Germline Variant in the MUTYHDNA Glycosylase Gene with Colorectal Adenoma Transformation into Malignancy

Background:MUTYHDNA glycosylase germline mutations are linkedto therecessive inheritanceof multiple adenoma. Studies have revealed that germline mutations in this gene are ethnicity related. This study aimed to identify the germline mutations in MUTYHgene and determine their prevalence among Jordanian patientswith colorectal adenoma. Methods: In this study, 150 colorectal adenoma patients and 150 cancer-free individuals with no previous history of polyps were recruited. Sanger DNA sequencing of the MUTYHgene(accession numberNG_008189.1)was carried out using 3130xL Genetic Analyzer. Sequencing results were analyzed by ChromasPro,and mutational effects were predicted by online bioinformatics tools. Results: Two novel variants, g.87C>T and c.1264G>C, wereidentified.g.87C>T was also found in 60 (40%) patients and 10 (6.7%) controls.However, c.1264G>C was detectedin 90 (60%) patients and 7 (4.7%) controls. Thus, a significant association was observedbetween these two variants and colorectal adenoma (pvalue for both variants was <0.0001). Moreover, the newly identified germline variant, c.1264G>C, was found to be significantly associated with colorectal adenoma transformation into malignancy (p< 0.0001). Conclusion:The data showed high prevalence of two germline mutations inMUTYH gene among Jordanians with colorectal adenoma, which may make them as potential early biomarkers for diagnosis of colorectal adenoma.