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FOLFIRINOX improves the prognosis of patients with PC; however, despite <jats:italic>UGT1A1<\/jats:italic> screening, adverse events, such as severe neutropenia, occur frequently. This study aimed to identify the novel biomarkers of severe neutropenia in patients treated with modified FOLFIRINOX (mFFX) for PC. In this study, patients with PC treated with mFFX (<jats:italic>n<\/jats:italic>\u2009=\u200971) and gemcitabine plus nab\u2010paclitaxel (GnP) (<jats:italic>n<\/jats:italic>\u2009=\u200992) and patients with colorectal cancer treated with FOLFOXIRI (<jats:italic>n<\/jats:italic>\u2009=\u200950) were included. Genome\u2010wide screening using whole\u2010exome sequencing was performed during the screening phase. Validation analysis was performed using polymerase chain reaction genotyping, the Cochran\u2013Armitage trend test, and multivariate analysis. The diagnostic performance of combined risk factors for severe neutropenia was examined using logistic regression with leave\u2010one\u2010out cross\u2010validation. Three gene polymorphisms were selected from the screening phase and subjected to the validation phase. In the validation phase, a single nucleotide polymorphism in <jats:italic>C11orf24<\/jats:italic> (c.448C&gt;T, rs901827) was significantly correlated with \u2265\u2009Grade 3 neutropenia in mFFX and FOLFOXIRI but not in GnP. Multivariate analysis showed <jats:italic>C11orf24<\/jats:italic> and baseline neutrophil count as independent risk factors for \u2265\u2009Grade 3 neutropenia. The diagnostic performance of the neutropenia prediction model showed areas under the curve of 0.754 (sensitivity\u2009=\u20090.605, specificity\u2009=\u20090.848) and 0.856 (sensitivity\u2009=\u20090.800, specificity\u2009=\u20090.893) for \u2265\u2009Grade 3 and 4 neutropenia, respectively. The <jats:italic>C11orf24<\/jats:italic> gene and baseline neutrophil count may be useful biomarkers for predicting severe neutropenia following irinotecan\u2010containing triplet chemotherapy.<\/jats:p>","DOI":"10.1111\/cas.70087","type":"journal-article","created":{"date-parts":[[2025,4,26]],"date-time":"2025-04-26T10:59:41Z","timestamp":1745665181000},"page":"2008-2019","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["The <i>C11orf24<\/i> Gene as a Useful Biomarker for Predicting Severe Neutropenia in Modified <scp>FOLFIRINOX<\/scp> for Pancreatic Cancer"],"prefix":"10.1111","volume":"116","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-7578-7577","authenticated-orcid":false,"given":"Gen","family":"Kanesada","sequence":"first","affiliation":[{"name":"Department of Gastroenterological, Breast and Endocrine Surgery Yamaguchi University Graduate School of Medicine  Ube Yamaguchi 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