PMID- 36974789
OWN - NLM
STAT- MEDLINE
DCOM- 20230405
LR  - 20230405
IS  - 1791-7530 (Electronic)
IS  - 0250-7005 (Linking)
VI  - 43
IP  - 4
DP  - 2023 Apr
TI  - Association of STAT3, CYP3A5, and ABCG2 Polymorphisms With Osimertinib-induced 
      Adverse Events in NSCLC Patients.
PG  - 1775-1783
LID - 10.21873/anticanres.16331 [doi]
AB  - BACKGROUND/AIM: Osimertinib is a key drug for treating epidermal growth factor 
      receptor (EGFR) mutation-positive non-small cell lung cancer (NSCLC). Genetic 
      differences may be associated to adverse events (AEs) induced by osimertinib. 
      This retrospective observational multicenter study evaluated the association of 
      genotypes, including STAT3 -1697C>G, CYP3A5 6986A>G, and ABCG2 421C>A, with the 
      incidence of osimertinib-induced AEs in patients with EGFR mutation-positive 
      NSCLC. PATIENTS AND METHODS: A total of 85 patients treated with osimertinib 
      (Institution A: 33 patients, Institution B: 52 patients) were enrolled in the 
      study. Single nucleotide polymorphisms were determined by real-time PCR, and the 
      incidence of AEs was compared for each genotype. RESULTS: Paronychia incidence 
      was 59% for the CC genotype, 19% for the CG genotype, and 19% for the GG genotype 
      at STAT3 -1697C>G. A genotype-related trend was observed (Cochran-Armitage test, 
      p=0.009). Multivariate analysis showed that the CC genotype at STAT3 -1697C>G and 
      female sex were significant independent factors associated with paronychia [odds 
      ratio (OR)=6.41, 95% confidence interval (CI)=1.94-21.20 and OR=3.40, 
      95%CI=1.03-11.22, respectively]. The incidence of diarrhea was 53% for the CC 
      genotype, 30% for the AC genotype, and 29% for the AA genotype at ABCG2 421C>A, 
      and a genotype-related trend was observed (p=0.048). However, the CC genotype at 
      ABCG2 421C>A was not a significant independent factor associated with diarrhea in 
      multivariate analysis. No significant associations were detected between other 
      polymorphisms and the incidence of AEs. CONCLUSION: STAT3 -1697C>G may be a novel 
      risk factor for osimertinib-induced paronychia in patients with NSCLC.
CI  - Copyright (c) 2023 International Institute of Anticancer Research (Dr. George J. 
      Delinasios), All rights reserved.
FAU - Tanda, Masaaki
AU  - Tanda M
AD  - Department of Pharmacy, Kobe University Hospital, Kobe, Japan.
FAU - Yamamoto, Kazuhiro
AU  - Yamamoto K
AD  - Department of Pharmacy, Kobe University Hospital, Kobe, Japan; 
      yamakz@med.kobe-u.ac.jp.
FAU - Hori, Tomoki
AU  - Hori T
AD  - Department of Pharmacy, Nara Prefecture General Medical Center, Nara, Japan.
FAU - Nishiguchi, Hiroki
AU  - Nishiguchi H
AD  - Department of Pharmacy, Kobe University Hospital, Kobe, Japan.
FAU - Yagi, Miki
AU  - Yagi M
AD  - Department of Pharmacy, Kobe University Hospital, Kobe, Japan.
FAU - Shimizu, Michiko
AU  - Shimizu M
AD  - Department of Pharmacy, Kobe University Hospital, Kobe, Japan.
FAU - Konishi, Toru
AU  - Konishi T
AD  - Department of Pharmacy, Kobe University Hospital, Kobe, Japan.
FAU - Ozaki, Tomonori
AU  - Ozaki T
AD  - Department of Pharmacy, Nara Prefecture General Medical Center, Nara, Japan.
FAU - Yoshioka, Natsue
AU  - Yoshioka N
AD  - Department of Pharmacy, Nara Prefecture General Medical Center, Nara, Japan.
FAU - Tachihara, Motoko
AU  - Tachihara M
AD  - Division of Respiratory Medicine, Department of Internal Medicine, Kobe 
      University Graduate School of Medicine, Kobe, Japan.
FAU - Ito, Takefumi
AU  - Ito T
AD  - Division of Respiratory Medicine, Nara Prefecture General Medical Center, Nara, 
      Japan.
FAU - Ikushima, Shigeki
AU  - Ikushima S
AD  - Department of Pharmacy, Nara Prefecture General Medical Center, Nara, Japan.
FAU - Omura, Tomohiro
AU  - Omura T
AD  - Department of Pharmacy, Kobe University Hospital, Kobe, Japan.
FAU - Yano, Ikuko
AU  - Yano I
AD  - Department of Pharmacy, Kobe University Hospital, Kobe, Japan.
LA  - eng
PT  - Journal Article
PT  - Multicenter Study
PT  - Observational Study
PL  - Greece
TA  - Anticancer Res
JT  - Anticancer research
JID - 8102988
RN  - 0 (ABCG2 protein, human)
RN  - 0 (Aniline Compounds)
RN  - 0 (Antineoplastic Agents)
RN  - EC 1.14.14.1 (CYP3A5 protein, human)
RN  - EC 1.14.14.1 (Cytochrome P-450 CYP3A)
RN  - EC 2.7.10.1 (ErbB Receptors)
RN  - 3C06JJ0Z2O (osimertinib)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 0 (STAT3 protein, human)
RN  - 0 (STAT3 Transcription Factor)
RN  - 0 (ATP Binding Cassette Transporter, Subfamily G, Member 2)
SB  - IM
MH  - Female
MH  - Humans
MH  - *Aniline Compounds/adverse effects/therapeutic use
MH  - *Antineoplastic Agents/adverse effects/therapeutic use
MH  - *Carcinoma, Non-Small-Cell Lung/drug therapy/genetics
MH  - Cytochrome P-450 CYP3A/genetics
MH  - Diarrhea/chemically induced
MH  - ErbB Receptors/genetics
MH  - *Lung Neoplasms/drug therapy/genetics
MH  - Mutation
MH  - *Paronychia/chemically induced
MH  - Polymorphism, Single Nucleotide
MH  - *Protein Kinase Inhibitors/adverse effects/therapeutic use
MH  - Retrospective Studies
MH  - STAT3 Transcription Factor/genetics
MH  - ATP Binding Cassette Transporter, Subfamily G, Member 2/genetics
OTO - NOTNLM
OT  - ABCG2
OT  - CYP3A5
OT  - Osimertinib
OT  - STAT3
OT  - adverse event
OT  - non-small cell lung cancer
OT  - polymorphism
EDAT- 2023/03/29 06:00
MHDA- 2023/03/29 06:05
CRDT- 2023/03/28 05:33
PHST- 2022/12/29 00:00 [received]
PHST- 2023/01/18 00:00 [revised]
PHST- 2023/01/27 00:00 [accepted]
PHST- 2023/03/29 06:05 [medline]
PHST- 2023/03/28 05:33 [entrez]
PHST- 2023/03/29 06:00 [pubmed]
AID - 43/4/1775 [pii]
AID - 10.21873/anticanres.16331 [doi]
PST - ppublish
SO  - Anticancer Res. 2023 Apr;43(4):1775-1783. doi: 10.21873/anticanres.16331.