ArticleCancer medicine2023
Association between a single nucleotide polymorphism in the R3HCC1 gene and irinotecan toxicity.
Article in Cancer medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed, 8 citations in OpenAlex.
- Article
- The C11orf24 Gene as a Useful Biomarker for Predicting Severe Neutropenia in Modified FOLFIRINOX for Pancreatic Cancer.Cancer science · 2025Article
- Parallel Toxicities: A Comparative Analysis of Chemotherapy-Induced Neutropenia and Alopecia.Cancers · 2025Review
- A Case of Inflammatory Myofibroblastic Tumor in the Abdominal Wall with Anaplastic Lymphoma Kinase and Whole Exome Sequencing Analysis.Surgical case reports · 2025Article
- Association between a single nucleotide polymorphism in the R3HCC1 gene and irinotecan toxicity.Cancer medicine · 2023Article
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Authors and funding
14 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveIrinotecan is a useful anticancer drug for colorectal cancer treatment. UGT1A1*28 and *6 gene polymorphisms are known risk factors for irinotecan-associated toxicity. However, severe adverse effects due to irinotecan have been observed even in patients who do not harbor UGT1A1*28 or *6. We investigated gene polymorphisms in the whole exome to identify useful biomarkers for irinotecan toxicity other than UGT1A.
methodsA total of 178 patients with metastatic colorectal cancer (mCRC) and 87 patients with pancreatic cancer were treated with FOLFIRI, FOLFOX, FOLFOXIRI, modified FOLFIRINOX, or gemcitabine plus nab-paclitaxel. Genome-wide screening was performed using whole-exome sequencing (WES), and validation analysis was performed using qPCR with a hydrolysis probe.
resultsUsing WES after a doublet chemotherapy regimen comprising irinotecan and 5-fluorouracil (n = 15), seven single nucleotide polymorphisms (SNPs) were identified as candidate biomarkers for irinotecan-associated toxicity of neutropenia. Among the seven SNPs, an SNP in R3H domain and coiled-coil containing 1 (R3HCC1; c.919G > A, rs2272761) showed a significant association with neutropenia (>grade 3) after doublet chemotherapy. Patients receiving irinotecan including triplet chemotherapy, FOLFOXIRI for mCRC (n = 23) or modified FOLFIRINOX for pancreatic cancer (n = 40), also showed significant linear trends between R3HCC1 polymorphism and neutropenia (p = 0.017 and 0.046, respectively). No significant association was observed in patients treated with irinotecan-free regimens, FOLFOX for mCRC (n = 66), and gemcitabine plus nab-paclitaxel for pancreatic cancer (n = 47).
conclusionThus, an SNP in the R3HCC1 gene may be a useful biomarker for the toxicity of irinotecan-containing chemotherapy for mCRC and pancreatic cancer.
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