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Oxidative Medicine and Cellular Longevity
Volume 2014 (2014), Article ID 617351, 12 pages
Research Article

Impaired 8-Hydroxyguanine Repair Activity of MUTYH Variant p.Arg109Trp Found in a Japanese Patient with Early-Onset Colorectal Cancer

1Department of Tumor Pathology, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi Ward, Hamamatsu, Shizuoka 431-3192, Japan
2Division of Cancer Development System, National Cancer Center Research Institute, Tokyo 104-0045, Japan
3Research Center for Environmental Quality Management, Kyoto University, Shiga 520-0811, Japan
4Department of Preventive Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan

Received 29 November 2013; Revised 5 February 2014; Accepted 11 February 2014; Published 23 March 2014

Academic Editor: Antonio Ayala

Copyright © 2014 Kazuya Shinmura et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Purpose. The biallelic inactivation of the 8-hydroxyguanine repair gene MUTYH leads to MUTYH-associated polyposis (MAP), which is characterized by colorectal multiple polyps and carcinoma(s). However, only limited information regarding MAP in the Japanese population is presently available. Since early-onset colorectal cancer (CRC) is a characteristic of MAP and might be caused by the inactivation of another 8-hydroxyguanine repair gene, OGG1, we investigated whether germline MUTYH and OGG1 mutations are involved in early-onset CRC in Japanese patients. Methods. Thirty-four Japanese patients with early-onset CRC were examined for germline MUTYH and OGG1 mutations using sequencing. Results. Biallelic pathogenic mutations were not found in any of the patients; however, a heterozygous p.Arg19*  MUTYH variant and a heterozygous p.Arg109Trp MUTYH variant were detected in one patient each. The p.Arg19* and p.Arg109Trp corresponded to p.Arg5* and p.Arg81Trp, respectively, in the type 2 nuclear-form protein. The defective DNA repair activity of p.Arg5* is apparent, while that of p.Arg81Trp has been demonstrated using DNA cleavage and supF forward mutation assays. Conclusion. These results suggest that biallelic MUTYH or OGG1 pathogenic mutations are rare in Japanese patients with early-onset CRC; however, the p.Arg19* and p.Arg109Trp MUTYH variants are associated with functional impairments.