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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The data that support the findings of this study are available from the corresponding author upon reasonable request.
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Acknowledgements
We appreciate all patients who participated in this study. The samples and data used for this study were provided from the BioBank Japan Project supported by the Japan Agency for Medical Research and Development (AMED) (Grant Number: JP19km0605001). This study was supported by grants from the Platform Program for Promotion of Genome Medicine funded by AMED (Grant Number: JP18km0405201). We express our gratitude to the staff of BioBank Japan for their assistance.
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KH, TO, MaK, and TM designed the study and analyzed and interpreted the data. KH wrote the paper. TO, CT, YK, YM, MiK, and TM performed the critical revision.
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Hikino, K., Ozeki, T., Koido, M. et al. Comparison of effects of UGT1A1*6 and UGT1A1*28 on irinotecan-induced adverse reactions in the Japanese population: analysis of the Biobank Japan Project. J Hum Genet 64, 1195–1202 (2019). https://doi.org/10.1038/s10038-019-0677-2
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DOI: https://doi.org/10.1038/s10038-019-0677-2
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