Genomics & Informatics

Korea Genome Organization (한국유전체학회)
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The UGT1A9*22 genotype identifies a high-risk group for irinotecan toxicity among gastric cancer patients

  • Lee, Choong-kun (Division of Medical Oncology, Yonsei Cancer Center, Yonsei University College of Medicine) ;
  • Chon, Hong Jae (Division of Medical Oncology, Yonsei Cancer Center, Yonsei University College of Medicine) ;
  • Kwon, Woo Sun (Brain Korea 21 Plus Project for Medical Science, Yonsei University College of Medicine) ;
  • Ban, Hyo-Jeong (KM Data Division, Korea Institute of Oriental Medicine) ;
  • Kim, Sang Cheol (Division of Healthcare and AI, Center for Precision Medicine, Korea National Institute of Health, Korea Centers for Disease Control and Prevention) ;
  • Kim, Hyunwook (Division of Medical Oncology, Yonsei Cancer Center, Yonsei University College of Medicine) ;
  • Jeung, Hei-Cheul (Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine) ;
  • Chung, Jimyung (Yonsei University Graduate School, Yonsei University College of Medicine) ;
  • Rha, Sun Young (Division of Medical Oncology, Yonsei Cancer Center, Yonsei University College of Medicine)
  • Received : 2022.08.22
  • Accepted : 2022.09.08
  • Published : 2022.09.30
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Abstract

Several studies have shown associations between irinotecan toxicity and UGT1A genetic variations in colorectal and lung cancer, but only limited data are available for gastric cancer patients. We evaluated the frequencies of UGT1A polymorphisms and their relationship with clinicopathologic parameters in 382 Korean gastric cancer patients. Polymorphisms of UGT1A1*6, UGT1A1*27, UGT1A1*28, UGT1A1*60, UGT1A7*2, UGT1A7*3, and UGT1A9*22 were genotyped by direct sequencing. In 98 patients treated with irinotecan-containing regimens, toxicity and response were compared according to the genotype. The UGT1A1*6 and UGT1A9*22 genotypes showed a higher prevalence in Korean gastric cancer patients, while the prevalence of the UG1A1*28 polymorphism was lower than in normal Koreans, as has been found in other studies of Asian populations. The incidence of severe diarrhea after irinotecan-containing treatment was more common in patients with the UGT1A1*6, UGT1A7*3 and UGT1A9*22 polymorphisms than in controls. The presence of the UGT1A1*6 allele also showed a significant association with grade III-IV neutropenia. Upon haplotype and diplotype analyses, almost every patient bearing the UGT1A1*6 or UGT1A7*3 variant also had the UGT1A9*22 polymorphism, and all severe manifestations of UGT1A polymorphism-associated toxicity were related to the UGT1A9*22 polymorphism. By genotyping UGT1A9*22 polymorphisms, we could identify high-risk gastric cancer patients receiving irinotecan-containing chemotherapy, who would experience severe toxicity. When treating high-risk patients with the UGT1A9*22 polymorphism, clinicians should closely monitor them for signs of toxicity such as severe diarrhea or neutropenia.

Keywords

Acknowledgement

This work was supported by a National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIT) (2020R1A2B5B02001452) and by a grant from the National R&D Program for Cancer Control, Ministry of Health and Welfare, Republic of Korea (HA15C0005).

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