Comparison of effects of UGT1A1*6 and UGT1A1*28 on irinotecan-induced adverse reactions in the Japanese population: analysis of the Biobank Japan Project

Keiko Hikino, Takeshi Ozeki, Masaru Koido, Chikashi Terao, Yoichiro Kamatani, Yoshinori Murakami, Michiaki Kubo, Taisei Mushiroda

Research output: Contribution to journalArticle

Abstract

It has been reported that there are differences in effects on irinotecan-induced adverse reactions between UGT1A1*6 and UGT1A1*28. In order to compare those differences in the Japanese population, we examined the associations between UGT1A1 and irinotecan-induced adverse reactions using the BioBank Japan Project database. We genotyped UTG1A1*6 and UGT1A1*28 and conducted case–control analyses. A total of 651 patients (102 cases and 549 tolerant controls) were included in this study. The results showed that UGT1A1*6/*6 is a predictor of adverse drug reactions (ADRs) (p-value 0.00070, odds ratio 6.59, 95% confidence interval 2.33–18.6), whereas UGT1A1*6/*28 and UGT1A1*28/*28 were not. The subanalysis comprising only patients with UGT1A1*6/*6, UGT1A1*6/*28, and UGT1A1*28/*28 revealed a trend towards an increased risk of ADRs in patients with UGT1A1*6 (p-value 0.0092, odds ratio 4.39, 95% confidence interval 1.57–14.9). Multiple logistic regression analyses showed that use of platinum-based antineoplastic drugs and presence of UGT1A1*6/*6 were independent variables, significantly associated with ADRs. The diagnostic performance of a predictive model had a sensitivity of 49.0%, specificity of 70.1%, and a number needed to screen of 5.8. We concluded that UGT1A1 testing could be useful to predict irinotecan-induced ADRs, and that UTG1A1*6 rather than UGT1A1*28 contributed to ADR occurrence.

Original languageEnglish
Pages (from-to)1195-1202
Number of pages8
JournalJournal of Human Genetics
Volume64
Issue number12
DOIs
Publication statusPublished - 01-12-2019

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irinotecan
Drug-Related Side Effects and Adverse Reactions
Japan
Population
Odds Ratio
Confidence Intervals
Platinum
Antineoplastic Agents
Logistic Models
Regression Analysis
Databases
Sensitivity and Specificity

All Science Journal Classification (ASJC) codes

  • Genetics
  • Genetics(clinical)

Cite this

Hikino, Keiko ; Ozeki, Takeshi ; Koido, Masaru ; Terao, Chikashi ; Kamatani, Yoichiro ; Murakami, Yoshinori ; Kubo, Michiaki ; Mushiroda, Taisei. / Comparison of effects of UGT1A1*6 and UGT1A1*28 on irinotecan-induced adverse reactions in the Japanese population : analysis of the Biobank Japan Project. In: Journal of Human Genetics. 2019 ; Vol. 64, No. 12. pp. 1195-1202.
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abstract = "It has been reported that there are differences in effects on irinotecan-induced adverse reactions between UGT1A1*6 and UGT1A1*28. In order to compare those differences in the Japanese population, we examined the associations between UGT1A1 and irinotecan-induced adverse reactions using the BioBank Japan Project database. We genotyped UTG1A1*6 and UGT1A1*28 and conducted case–control analyses. A total of 651 patients (102 cases and 549 tolerant controls) were included in this study. The results showed that UGT1A1*6/*6 is a predictor of adverse drug reactions (ADRs) (p-value 0.00070, odds ratio 6.59, 95{\%} confidence interval 2.33–18.6), whereas UGT1A1*6/*28 and UGT1A1*28/*28 were not. The subanalysis comprising only patients with UGT1A1*6/*6, UGT1A1*6/*28, and UGT1A1*28/*28 revealed a trend towards an increased risk of ADRs in patients with UGT1A1*6 (p-value 0.0092, odds ratio 4.39, 95{\%} confidence interval 1.57–14.9). Multiple logistic regression analyses showed that use of platinum-based antineoplastic drugs and presence of UGT1A1*6/*6 were independent variables, significantly associated with ADRs. The diagnostic performance of a predictive model had a sensitivity of 49.0{\%}, specificity of 70.1{\%}, and a number needed to screen of 5.8. We concluded that UGT1A1 testing could be useful to predict irinotecan-induced ADRs, and that UTG1A1*6 rather than UGT1A1*28 contributed to ADR occurrence.",
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Comparison of effects of UGT1A1*6 and UGT1A1*28 on irinotecan-induced adverse reactions in the Japanese population : analysis of the Biobank Japan Project. / Hikino, Keiko; Ozeki, Takeshi; Koido, Masaru; Terao, Chikashi; Kamatani, Yoichiro; Murakami, Yoshinori; Kubo, Michiaki; Mushiroda, Taisei.

In: Journal of Human Genetics, Vol. 64, No. 12, 01.12.2019, p. 1195-1202.

Research output: Contribution to journalArticle

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T1 - Comparison of effects of UGT1A1*6 and UGT1A1*28 on irinotecan-induced adverse reactions in the Japanese population

T2 - analysis of the Biobank Japan Project

AU - Hikino, Keiko

AU - Ozeki, Takeshi

AU - Koido, Masaru

AU - Terao, Chikashi

AU - Kamatani, Yoichiro

AU - Murakami, Yoshinori

AU - Kubo, Michiaki

AU - Mushiroda, Taisei

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