Evaluation of the associations of interlukin-7 genetic variants with toxicity and efficacy of immune checkpoint inhibitors: A replication study of a Japanese population, based on the findings of a European genome-wide association study.
drug‐related side‐effects and adverse reactions
hepatocellular carcinoma
immune checkpoint inhibitors
interleukin‐7
single‐nucleotide polymorphism
treatment efficacy
Journal
Hepatology research : the official journal of the Japan Society of Hepatology
ISSN: 1386-6346
Titre abrégé: Hepatol Res
Pays: Netherlands
ID NLM: 9711801
Informations de publication
Date de publication:
11 Jul 2024
11 Jul 2024
Historique:
revised:
05
06
2024
received:
25
04
2024
accepted:
24
06
2024
medline:
11
7
2024
pubmed:
11
7
2024
entrez:
11
7
2024
Statut:
aheadofprint
Résumé
Recent genome-wide association studies of European populations have identified rs16906115, a single-nucleotide polymorphism in the interleukin-7 gene, as a predictor of immune-related adverse events (irAEs) and the therapeutic efficacy of immune checkpoint inhibitors. We evaluated this single-nucleotide polymorphism in a Japanese population. From January 2021, we stored host DNA from individuals who received various types of immune checkpoint inhibitors. From this population, we categorized 510 participants into cases (grade ≥2 irAEs) and controls (received ≥3 immune checkpoint inhibitor doses, follow-up ≥12 weeks, no irAEs), and divided 339 hepatocellular carcinoma patients treated with atezolizumab/bevacizumab into responders and non-responders, evaluated using the modified response evaluation criteria in solid tumors. We compared the minor allele frequencies of rs16906115 between cases and controls, and responders and non-responders. In the irAE prediction analysis of 234 cases and 276 controls, the minor allele frequency was 0.244 in the case group and 0.265 in the control group. This difference is not significant. In the analysis predicting the therapeutic efficacy for hepatocellular carcinoma patients, the responders had a significantly lower minor allele frequency of 0.220, compared with 0.300 for the non-responders (p = 0.022). Univariate and multivariate analyses identified the minor allele homozygosity as a significant predictor of treatment response, with odds ratios of 0.292 (p = 0.015) in the univariate analysis and 0.315 (p = 0.023) in the multivariate analysis. In our Japanese cohort, no association was found between the rs16906115 minor allele and irAEs or treatment efficacy. The minor allele homozygosity may be associated with a negative therapeutic outcome. UMIN Clinical Trials Registry with the number UMIN000043798.
Types de publication
Journal Article
Langues
eng
Subventions
Organisme : Japan Agency for Medical Research and Development
Organisme : Japan Society for the Promotion of Science
Informations de copyright
© 2024 Japan Society of Hepatology.
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