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The DOI matches its Crossref record; 26 of the 26 references it cites were found in a registry or an index.

Genetic Variants in the UDP-glucuronosyltransferase 1A1 Gene Predict the Risk of Severe Neutropenia of Irinotecan

Open access
Innocenti, Federico, Undevia, Samir D., Iyer, Lalitha, Xian Chen, Pei, Das, Soma, Kocherginsky, Masha, Karrison, Theodore, Janisch, Linda, Ramírez, Jacqueline, Rudin, Charles M., Vokes, Everett E., Ratain, Mark J.·2004·Journal of Clinical Oncology
DOI 10.1200/jco.2004.07.173
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Abstract

Purpose: Severe toxicity is commonly observed in cancer patients receiving irinotecan. UDP-glucuronosyltransferase 1A1 (UGT1A1) catalyzes the glucuronidation of the active metabolite SN-38. This study prospectively evaluated the association between the prevalence of severe toxicity and UGT1A1 genetic variation. Patients and Methods: Sixty-six cancer patients with advanced disease refractory to other treatments received irinotecan 350 mg/m 2 every 3 weeks. Toxicity and pharmacokinetic data were measured during cycle 1. UGT1A1 variants (−3279G>T, −3156G>A, promoter TA indel, 211G>A, 686C>A) were genotyped. Results: The prevalence of grade 4 neutropenia was 9.5%. Grade 4 neutropenia was much more common in patients with the TA indel 7/7 genotype (3 of 6 patients; 50%) compared with 6/7 (3 of 24 patients; 12.5%) and 6/6 (0 of 29 patients; 0%) (P = .001). The TA indel genotype was significantly associated with the absolute neutrophil count nadir (7/7 < 6/7 < 6/6, P = .02). The relative risk of grade 4 neutropenia was 9.3 (95% CI, 2.4 to 36.4) for the 7/7 patients versus the rest of the patients. Pretreatment total bilirubin levels (mean ± standard deviation) were significantly higher in patients with grade 4 neutropenia (0.83 ± 0.08 mg/dL) compared to those without grade 4 neutropenia (0.47 ± 0.03 mg/dL; P < .001). The −3156G>A variant seemed to distinguish different phenotypes of total bilirubin within the TA indel genotypes. The −3156 genotype and the SN-38 area under the concentration versus time curve were significant predictors of ln(absolute neutrophil count nadir; r 2 = 0.51). Conclusion: UGT1A1 genotype and total bilirubin levels are strongly associated with severe neutropenia, and could be used to identify cancer patients predisposed to the severe toxicity of irinotecan. The hypothesis that the −3156G>A variant is a better predictor of UGT1A1 status than the previously reported TA indel requires further testing.

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Metadata

Authors
Innocenti, F., Undevia, S. D., Iyer, L., Xian Chen, P., Das, S., Kocherginsky, M., Karrison, T., Janisch, L., Ramírez, J., Rudin, C. M., Vokes, E. E., & Ratain, M. J.
Venue
Journal of Clinical Oncology
Publisher
American Society of Clinical Oncology (ASCO)
Published
2004-04-15
Volume
22
Issue
8
Pages
1382-1388
ISSN
  • 0732-183X (ISSN-L)
  • 1527-7755
DOI
10.1200/jco.2004.07.173
OpenAlex
W2095822339
Cited by
964
References
26
FWCI
51.53
Type
journal article
Language
en
Open access
bronze

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CoChat. (2026). Citation check: Genetic Variants in the UDP-glucuronosyltransferase 1A1 Gene Predict the Risk of Severe Neutropenia of Irinotecan. https://app.cochat.ai/papers/10.1200/jco.2004.07.173
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Innocenti, F., Undevia, S. D., Iyer, L., Xian Chen, P., Das, S., Kocherginsky, M., Karrison, T., Janisch, L., Ramírez, J., Rudin, C. M., Vokes, E. E., & Ratain, M. J. (2004). Genetic Variants in the UDP-glucuronosyltransferase 1A1 Gene Predict the Risk of Severe Neutropenia of Irinotecan. Journal of Clinical Oncology. https://doi.org/10.1200/jco.2004.07.173

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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.