ArticleEuropean journal of cancer (Oxford, England : 1990)2024
PCCA variant rs16957301 is a novel AKI risk genotype-specific for patients who receive ICI treatment: Real-world evidence from all of us cohort.
Article in European journal of cancer (Oxford, England : 1990), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed.
- Insight into Genome-Wide Associations of Growth Trajectories Using a Hierarchical Non-Linear Mixed Model.Biology · 2026Article
- Immune checkpoint inhibitor exposure and outcomes of gastrointestinal bleeding in cancer patients: a national analysis of 130,557 hospitalizations, 2018-2022.Frontiers in medicine · 2026Article
- Risk stratification for immune checkpoint inhibitor rechallenge after acute kidney injury: towards a precision medicine framework.Frontiers in immunology · 2026Review
- A spatiotemporal state-inference framework for adaptive immunotherapy in glioblastoma.Frontiers in oncology · 2026Review
- Prognostic Factors Analysis in Patients with Hepatocellular Carcinoma Receiving PD-1/PD-L1 Inhibitors.Journal of hepatocellular carcinoma · 2026Article
- Urgent considerations on renal immune-related adverse events in oncology practice.Frontiers in immunology · 2025Review
- Deep Learning-Based Automatic Segmentation Combined with Radiomics to Predict Post-TACE Liver Failure in HCC Patients.Journal of hepatocellular carcinoma · 2024Article
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Abstract
introductionImmune checkpoint inhibitors (ICIs) enhance the immune system's ability to target and destroy cancer cells, but can also trigger immune-related adverse events (irAEs), such as acute kidney injury (ICI-AKI), complicating patient management. Limited knowledge of genetic predispositions to ICI-AKI highlights the need for genomic studies to improve therapeutic strategies.
objectiveTo identify genetic predispositions for ICI-AKI using large-scale real-world data.
methodsA systematic literature search led to 14 candidate variants related to irAEs. We performed a candidate variant association study with these variants using the All of Us cohort. An ICI-treated cohort and a general cohort were established to evaluate ICI-AKI risk. Logistic regression, adjusted for sex, evaluated the impact of each candidate genotype, separately for self-reported and ancestry-estimated race. Kaplan-Meier survival analysis assessed genetic effects on AKI-free survival.
resultsThe ICI cohort (n = 414) showed a one-year AKI incidence rate of 23.2 %, significantly higher than the general cohort (6.5 %, n = 213,282). The rs16957301 variant (chr13:100324308, T > C) in the PCCA gene was a significant risk genotype for ICI-AKI among self-reported White (Beta=0.93, CI: 0.32 - 1.54, ORs= 2.53, Bonferroni-corrected P-value=0.047) and ancestry estimated Europeans (Beta = 0.94, CI: 0.31 - 1.57, ORs= 2.56, Bonferroni-corrected P-value=0.044). Self-reported White with the rs16957301 risk genotypes (TC/CC) developed AKI significantly earlier (3.6 months) compared to the reference genotype (TT, 7.0 months, log-rank P = 0.04). Consistent results were found in ancestry-estimated Europeans. This variant did not present significant AKI risks in the general cohort (Beta: -0.008-0.035, FDR: 0.75-0.99).
conclusionOur findings suggest that rs16957301 in PCCA may serve as an ICI-AKI risk marker in Caucasians. Further studies are needed to validate this association and explore risks in other populations.
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