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Association between a single nucleotide polymorphism in the R3HCC1 gene and irinotecan toxicity.
- Source :
-
Cancer medicine [Cancer Med] 2023 Feb; Vol. 12 (4), pp. 4294-4305. Date of Electronic Publication: 2022 Oct 29. - Publication Year :
- 2023
-
Abstract
- 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.<br />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.<br />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).<br />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.<br /> (© 2022 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)
- Subjects :
- Humans
Irinotecan
Polymorphism, Single Nucleotide
Camptothecin adverse effects
Antineoplastic Combined Chemotherapy Protocols adverse effects
Fluorouracil
Leucovorin adverse effects
Pancreatic Neoplasms
Pancreatic Neoplasms drug therapy
Pancreatic Neoplasms genetics
Colorectal Neoplasms drug therapy
Colorectal Neoplasms genetics
Colorectal Neoplasms pathology
Colonic Neoplasms drug therapy
Neutropenia chemically induced
Rectal Neoplasms drug therapy
Subjects
Details
- Language :
- English
- ISSN :
- 2045-7634
- Volume :
- 12
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Cancer medicine
- Publication Type :
- Academic Journal
- Accession number :
- 36308049
- Full Text :
- https://doi.org/10.1002/cam4.5299