Comparison of effects of UGT1A16 and UGT1A128 on irinotecan-induced adverse reactions in the Japanese population: analysis of the Biobank Japan Project

• Published in: Journal of human genetics 2019-12, Vol.64 (12), p.1195-1202
• Main Authors: Hikino, Keiko, Ozeki, Takeshi, Koido, Masaru, Terao, Chikashi, Kamatani, Yoichiro, Murakami, Yoshinori, Kubo, Michiaki, Mushiroda, Taisei
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Antineoplastic Agents - adverse effects; Antineoplastic drugs; Asian people; Asians - genetics; Biological Specimen Banks; Cancer therapies; Case-Control Studies; Chemotherapy; Confidence intervals; Drug-Related Side Effects and Adverse Reactions - genetics; Female; Gastric cancer; Genetics; Genotype; Glucuronosyltransferase - genetics; Humans; Irinotecan; Irinotecan - adverse effects; Japan; Laboratories; Lung cancer; Male; Middle Aged; Neutropenia; Platinum; Polymorphism, Genetic - genetics; Population; Prediction models; Side effects; Studies
• ISSN: 1434-5161; 1435-232X
• DOI: 10.1038/s10038-019-0677-2

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.