Pancreatic cancer (PC) is an aggressive and lethal tumor with a poor prognosis. FOLFIRINOX improves the prognosis of patients with PC; however, despite UGT1A1 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 (n = 71) and gemcitabine plus nab-paclitaxel (GnP) (n = 92) and patients with colorectal cancer treated with FOLFOXIRI (n = 50) were included. Genome-wide screening using whole-exome sequencing was performed during the screening phase. Validation analysis was performed using polymerase chain reaction genotyping, the Cochran-Armitage trend test, and multivariate analysis. The diagnostic performance of combined risk factors for severe neutropenia was examined using logistic regression with leave-one-out cross-validation. Three gene polymorphisms were selected from the screening phase and subjected to the validation phase. In the validation phase, a single nucleotide polymorphism in C11orf24 (c.448C>T, rs901827) was significantly correlated with ≥ Grade 3 neutropenia in mFFX and FOLFOXIRI but not in GnP. Multivariate analysis showed C11orf24 and baseline neutrophil count as independent risk factors for ≥ Grade 3 neutropenia. The diagnostic performance of the neutropenia prediction model showed areas under the curve of 0.754 (sensitivity = 0.605, specificity = 0.848) and 0.856 (sensitivity = 0.800, specificity = 0.893) for ≥ Grade 3 and 4 neutropenia, respectively. The C11orf24 gene and baseline neutrophil count may be useful biomarkers for predicting severe neutropenia following irinotecan-containing triplet chemotherapy.
