{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T22:07:52Z","timestamp":1779401272165,"version":"3.53.1"},"reference-count":55,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2022,10,29]],"date-time":"2022-10-29T00:00:00Z","timestamp":1667001600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["KAKENHI 21K08799"],"award-info":[{"award-number":["KAKENHI 21K08799"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["KAKENHI 22K08849"],"award-info":[{"award-number":["KAKENHI 22K08849"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2023,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Irinotecan is a useful anticancer drug for colorectal cancer treatment. <jats:italic>UGT1A1*28<\/jats:italic> and <jats:italic>*6<\/jats:italic> gene polymorphisms are known risk factors for irinotecan\u2010associated toxicity. However, severe adverse effects due to irinotecan have been observed even in patients who do not harbor <jats:italic>UGT1A1*28<\/jats:italic> or <jats:italic>*6<\/jats:italic>. We investigated gene polymorphisms in the whole exome to identify useful biomarkers for irinotecan toxicity other than <jats:italic>UGT1A<\/jats:italic>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>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\u2010paclitaxel. Genome\u2010wide screening was performed using whole\u2010exome sequencing (WES), and validation analysis was performed using qPCR with a hydrolysis probe.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Using WES after a doublet chemotherapy regimen comprising irinotecan and 5\u2010fluorouracil (<jats:italic>n<\/jats:italic>\u00a0=\u00a015), seven single nucleotide polymorphisms (SNPs) were identified as candidate biomarkers for irinotecan\u2010associated toxicity of neutropenia. Among the seven SNPs, an SNP in R3H domain and coiled\u2010coil containing 1 (<jats:italic>R3HCC1<\/jats:italic>; c.919G\u2009&gt;\u2009A, rs2272761) showed a significant association with neutropenia (&gt;grade 3) after doublet chemotherapy. Patients receiving irinotecan including triplet chemotherapy, FOLFOXIRI for mCRC (<jats:italic>n<\/jats:italic>\u00a0=\u00a023) or modified FOLFIRINOX for pancreatic cancer (<jats:italic>n<\/jats:italic>\u00a0=\u00a040), also showed significant linear trends between <jats:italic>R3HCC1<\/jats:italic> polymorphism and neutropenia (<jats:italic>p<\/jats:italic>\u00a0=\u00a00.017 and 0.046, respectively). No significant association was observed in patients treated with irinotecan\u2010free regimens, FOLFOX for mCRC (<jats:italic>n<\/jats:italic>\u00a0=\u00a066), and gemcitabine plus nab\u2010paclitaxel for pancreatic cancer (<jats:italic>n<\/jats:italic>\u00a0=\u00a047).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Thus, an SNP in the <jats:italic>R3HCC1<\/jats:italic> gene may be a useful biomarker for the toxicity of irinotecan\u2010containing chemotherapy for mCRC and pancreatic cancer.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cam4.5299","type":"journal-article","created":{"date-parts":[[2022,10,29]],"date-time":"2022-10-29T07:39:37Z","timestamp":1667029177000},"page":"4294-4305","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Association between a single nucleotide polymorphism in the <i>R3HCC1<\/i> gene and irinotecan 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