論文

査読有り 国際誌
2022年10月29日

Association between a single nucleotide polymorphism in the R3HCC1 gene and irinotecan toxicity.

Cancer medicine
  • Kou Kanesada
  • Ryouichi Tsunedomi
  • Shoichi Hazama
  • Hiroyuki Ogihara
  • Yoshihiko Hamamoto
  • Yoshitaro Shindo
  • Hiroto Matsui
  • Yukio Tokumitsu
  • Shin Yoshida
  • Michihisa Iida
  • Nobuaki Suzuki
  • Shigeru Takeda
  • Tatsuya Ioka
  • Hiroaki Nagano
  • 全て表示

12
4
開始ページ
4294
終了ページ
4305
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1002/cam4.5299

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.

リンク情報
DOI
https://doi.org/10.1002/cam4.5299
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/36308049
PubMed Central
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9972014
ID情報
  • DOI : 10.1002/cam4.5299
  • PubMed ID : 36308049
  • PubMed Central 記事ID : PMC9972014

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