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D‑amino acid oxidase (DAO) rare genetic missense variant p.Pro103Leu and gastric cancer

  • Authors:
    • Yuan Zong
    • Masashi Tanaka
    • Masaaki Muramatsu
    • Tomio Arai
  • View Affiliations / Copyright

    Affiliations: Department of Molecular Epidemiology, Medical Research Institute, Tokyo Medical and Dental University, Bunkyo‑ku, Tokyo 113‑8510, Japan, Department of Pathology, Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology, Itabashi‑ku, Tokyo 173‑0015, Japan
    Copyright: © Zong et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 58
    |
    Published online on: January 24, 2021
       https://doi.org/10.3892/mco.2021.2220
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Abstract

Gastric cancer is prevalent in the Asian population. Genetic predisposition to gastric cancer is not fully understood. Recent studies have demonstrated that D‑amino acid oxidase (DAO), a multifunctional enzyme, protects the mucosa of gastrointestinal (GI) tracts by generating hydrogen sulfide (H2S) in the stomach of rodents. The present study surveyed rare germline variants in the human DAO gene with regard to the incidence of gastric cancer. The consecutive autopsy cases registered in the JG‑SNP database (n=2,343; mean age, 80 years) were employed and genotyped with Exome Bead‑Chips. There were three non‑synonymous rare variants, p.R22H, p.P103L and p.R283Q, of which the minor allele frequencies were 0.09, 0.21 and 0.02%, respectively. Carriers of these variants were surveyed, the results of which revealed that 4 out of 10 patients with the p.P103L variant had gastric cancer (Fisher's exact test, P=0.018). All 4 patients were men with drinking and smoking habits. Among the other 6 women, there was one incidence of small intestine cancer and one of colon cancer. Neither p.R22H nor p.R283Q carriers had GI cancer. DAO p.P103L is reported to be a modifier of amyotrophic lateral sclerosis (ALS) and may potentially be a hypomorphic allele. Thus, it is hypothesized that this rare variant might have affected protection against gastric mucosal damage through H2S signaling in the mucosa, which leads to high prevalence of gastric cancer. The role of rare variant DAO p.P103L warrants further investigation in larger cohorts.
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Copy and paste a formatted citation
Spandidos Publications style
Zong Y, Tanaka M, Muramatsu M and Arai T: D‑amino acid oxidase (DAO) rare genetic missense variant p.Pro103Leu and gastric cancer. Mol Clin Oncol 14: 58, 2021.
APA
Zong, Y., Tanaka, M., Muramatsu, M., & Arai, T. (2021). D‑amino acid oxidase (DAO) rare genetic missense variant p.Pro103Leu and gastric cancer. Molecular and Clinical Oncology, 14, 58. https://doi.org/10.3892/mco.2021.2220
MLA
Zong, Y., Tanaka, M., Muramatsu, M., Arai, T."D‑amino acid oxidase (DAO) rare genetic missense variant p.Pro103Leu and gastric cancer". Molecular and Clinical Oncology 14.3 (2021): 58.
Chicago
Zong, Y., Tanaka, M., Muramatsu, M., Arai, T."D‑amino acid oxidase (DAO) rare genetic missense variant p.Pro103Leu and gastric cancer". Molecular and Clinical Oncology 14, no. 3 (2021): 58. https://doi.org/10.3892/mco.2021.2220
Copy and paste a formatted citation
x
Spandidos Publications style
Zong Y, Tanaka M, Muramatsu M and Arai T: D‑amino acid oxidase (DAO) rare genetic missense variant p.Pro103Leu and gastric cancer. Mol Clin Oncol 14: 58, 2021.
APA
Zong, Y., Tanaka, M., Muramatsu, M., & Arai, T. (2021). D‑amino acid oxidase (DAO) rare genetic missense variant p.Pro103Leu and gastric cancer. Molecular and Clinical Oncology, 14, 58. https://doi.org/10.3892/mco.2021.2220
MLA
Zong, Y., Tanaka, M., Muramatsu, M., Arai, T."D‑amino acid oxidase (DAO) rare genetic missense variant p.Pro103Leu and gastric cancer". Molecular and Clinical Oncology 14.3 (2021): 58.
Chicago
Zong, Y., Tanaka, M., Muramatsu, M., Arai, T."D‑amino acid oxidase (DAO) rare genetic missense variant p.Pro103Leu and gastric cancer". Molecular and Clinical Oncology 14, no. 3 (2021): 58. https://doi.org/10.3892/mco.2021.2220
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