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The UGT1A9*22 genotype identifies a high-risk group for irinotecan toxicity among gastric cancer patients

 Choong-Kun Lee  ;  Hong Jae Chon  ;  Woo Sun Kwon  ;  Hyo-Jeong Ban  ;  Sang Cheol Kim  ;  Hyunwook Kim  ;  Hei-Cheul Jeung  ;  Jimyung Chung  ;  Sun Young Rha 
 Genomics & Informatics, Vol.20(3) : e29, 2022-09 
Journal Title
Genomics & Informatics
Issue Date
DNA polymorphism ; UGT1A9*22 ; gastric neoplasms ; irinotecan ; toxicity
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 severe toxicity such as intense diarrhea or neutropenia.
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1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Kwon, Woo Sun(권우선) ORCID logo https://orcid.org/0000-0003-0268-5624
Kim, Hyun Wook(김현욱) ORCID logo https://orcid.org/0000-0002-4274-7562
Rha, Sun Young(라선영) ORCID logo https://orcid.org/0000-0002-2512-4531
Lee, Choong-kun(이충근) ORCID logo https://orcid.org/0000-0001-5151-5096
Chon, Hong Jae(전홍재)
Jeung, Hei Cheul(정희철) ORCID logo https://orcid.org/0000-0003-0952-3679
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