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http://purl.uniprot.org/citations/36308049http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/36308049http://www.w3.org/2000/01/rdf-schema#comment"

Objective

Irinotecan 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.

Methods

A 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.

Results

Using 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).

Conclusion

Thus, an SNP in the R3HCC1 gene may be a useful biomarker for the toxicity of irinotecan-containing chemotherapy for mCRC and pancreatic cancer."xsd:string
http://purl.uniprot.org/citations/36308049http://purl.org/dc/terms/identifier"doi:10.1002/cam4.5299"xsd:string
http://purl.uniprot.org/citations/36308049http://purl.uniprot.org/core/author"Matsui H."xsd:string
http://purl.uniprot.org/citations/36308049http://purl.uniprot.org/core/author"Nagano H."xsd:string
http://purl.uniprot.org/citations/36308049http://purl.uniprot.org/core/author"Takeda S."xsd:string
http://purl.uniprot.org/citations/36308049http://purl.uniprot.org/core/author"Yoshida S."xsd:string
http://purl.uniprot.org/citations/36308049http://purl.uniprot.org/core/author"Suzuki N."xsd:string
http://purl.uniprot.org/citations/36308049http://purl.uniprot.org/core/author"Iida M."xsd:string
http://purl.uniprot.org/citations/36308049http://purl.uniprot.org/core/author"Shindo Y."xsd:string
http://purl.uniprot.org/citations/36308049http://purl.uniprot.org/core/author"Ioka T."xsd:string
http://purl.uniprot.org/citations/36308049http://purl.uniprot.org/core/author"Hamamoto Y."xsd:string
http://purl.uniprot.org/citations/36308049http://purl.uniprot.org/core/author"Ogihara H."xsd:string
http://purl.uniprot.org/citations/36308049http://purl.uniprot.org/core/author"Hazama S."xsd:string
http://purl.uniprot.org/citations/36308049http://purl.uniprot.org/core/author"Tokumitsu Y."xsd:string
http://purl.uniprot.org/citations/36308049http://purl.uniprot.org/core/author"Tsunedomi R."xsd:string
http://purl.uniprot.org/citations/36308049http://purl.uniprot.org/core/author"Kanesada K."xsd:string
http://purl.uniprot.org/citations/36308049http://purl.uniprot.org/core/date"2023"xsd:gYear
http://purl.uniprot.org/citations/36308049http://purl.uniprot.org/core/name"Cancer Med"xsd:string
http://purl.uniprot.org/citations/36308049http://purl.uniprot.org/core/pages"4294-4305"xsd:string
http://purl.uniprot.org/citations/36308049http://purl.uniprot.org/core/title"Association between a single nucleotide polymorphism in the R3HCC1 gene and irinotecan toxicity."xsd:string
http://purl.uniprot.org/citations/36308049http://purl.uniprot.org/core/volume"12"xsd:string
http://purl.uniprot.org/citations/36308049http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/36308049
http://purl.uniprot.org/citations/36308049http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/36308049
http://purl.uniprot.org/uniprot/#_B4DE49-mappedCitation-36308049http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/36308049
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