PMID- 36070895
OWN - NLM
STAT- MEDLINE
DCOM- 20221028
LR  - 20221028
IS  - 1349-3329 (Electronic)
IS  - 0040-8727 (Linking)
VI  - 258
IP  - 3
DP  - 2022 Oct 25
TI  - Decreased Expression of NRF2 Target Genes after Alcohol Exposure in the 
      Background Esophageal Mucosa of Patients with Esophageal Squamous Cell Carcinoma.
PG  - 195-206
LID - 10.1620/tjem.2022.J077 [doi]
AB  - Patients with esophageal squamous cell carcinoma (ESCC) might have a specific 
      mechanism for the carcinogenesis by alcohol consumption in the background 
      esophageal mucosa, and nuclear factor erythroid 2-related factor 2 (NRF2), which 
      plays a protective role against esophageal carcinogenesis, and barrier 
      dysfunction might be associated with this phenomenon. This study aimed to confirm 
      this hypothesis. Twenty patients with superficial ESCCs (ESCC patients) and 20 
      age- and sex-matched patients without ESCC (non-ESCC patients) were enrolled. 
      Biopsy samples were obtained from non-neoplastic esophageal mucosa: one for 
      histological evaluation, one for quantitative real-time polymerase chain reaction 
      (PCR), and two for the mini-Ussing chamber system to measure transepithelial 
      electrical resistance (TEER) and, thereafter, for PCR. The TEER after 
      acetaldehyde or both acetaldehyde and ethanol exposure did not differ 
      significantly between ESCC and non-ESCC patients. Unlike non-ESCC patients, mRNA 
      levels of NRF2 target genes and claudin4 in ESCC patients tended to decrease 
      after the exposure, with a significant difference between no exposure and both 
      acetaldehyde and ethanol exposure in NRF2 target genes (p < 0.05). Furthermore, 
      in ESCC patients, the decreased tendency of mRNA levels of NRF2 target genes 
      after the exposure was more pronounced in high-risk states, such as aldehyde 
      dehydrogenase 2 (ALDH2) Lys alleles (Glu/Lys + Lys/Lys), Lugol-voiding lesion 
      grade C, and drinking history. In conclusion, the protective role of NRF2 against 
      carcinogenesis from alcohol exposure might be disrupted in the background 
      esophageal mucosa of ESCC patients, which might lead to a high incidence of 
      metachronous ESCC.
FAU - Toda, Shusuke
AU  - Toda S
AD  - Division of Gastroenterology, Tohoku University Graduate School of Medicine.
FAU - Hatta, Waku
AU  - Hatta W
AD  - Division of Gastroenterology, Tohoku University Graduate School of Medicine.
FAU - Asanuma, Kiyotaka
AU  - Asanuma K
AD  - Division of Gastroenterology, Tohoku University Graduate School of Medicine.
FAU - Asano, Naoki
AU  - Asano N
AD  - Division of Gastroenterology, Tohoku University Graduate School of Medicine.
FAU - Ono, Yoshitaka
AU  - Ono Y
AD  - Division of Gastroenterology, Tohoku University Graduate School of Medicine.
FAU - Abe, Hiroko
AU  - Abe H
AD  - Division of Gastroenterology, Tohoku University Graduate School of Medicine.
FAU - Ogata, Yohei
AU  - Ogata Y
AD  - Division of Gastroenterology, Tohoku University Graduate School of Medicine.
FAU - Saito, Masahiro
AU  - Saito M
AD  - Division of Gastroenterology, Tohoku University Graduate School of Medicine.
FAU - Kanno, Takeshi
AU  - Kanno T
AD  - Division of Gastroenterology, Tohoku University Graduate School of Medicine.
FAU - Jin, Xiaoyi
AU  - Jin X
AD  - Division of Gastroenterology, Tohoku University Graduate School of Medicine.
FAU - Uno, Kaname
AU  - Uno K
AD  - Division of Gastroenterology, Tohoku University Graduate School of Medicine.
FAU - Koike, Tomoyuki
AU  - Koike T
AD  - Division of Gastroenterology, Tohoku University Graduate School of Medicine.
FAU - Imatani, Akira
AU  - Imatani A
AD  - Division of Gastroenterology, Tohoku University Graduate School of Medicine.
FAU - Hamada, Shin
AU  - Hamada S
AD  - Division of Gastroenterology, Tohoku University Graduate School of Medicine.
FAU - Nakamura, Tomohiro
AU  - Nakamura T
AD  - Department of Health Record Informatics, Tohoku Medical Megabank Organization, 
      Tohoku University.
FAU - Nakaya, Naoki
AU  - Nakaya N
AD  - Department of Preventive Medicine and Epidemiology, Tohoku Medical Megabank 
      Organization, Tohoku University.
FAU - Masamune, Atsushi
AU  - Masamune A
AD  - Division of Gastroenterology, Tohoku University Graduate School of Medicine.
LA  - eng
PT  - Journal Article
DEP - 20220908
PL  - Japan
TA  - Tohoku J Exp Med
JT  - The Tohoku journal of experimental medicine
JID - 0417355
RN  - EC 1.2.1.3 (Aldehyde Dehydrogenase, Mitochondrial)
RN  - 0 (NF-E2-Related Factor 2)
RN  - 0 (Claudin-4)
RN  - 3K9958V90M (Ethanol)
RN  - GO1N1ZPR3B (Acetaldehyde)
RN  - 0 (RNA, Messenger)
RN  - EC 1.2.1.3 (ALDH2 protein, human)
SB  - IM
MH  - Humans
MH  - *Esophageal Squamous Cell Carcinoma/genetics
MH  - Esophageal Mucosa/metabolism/pathology
MH  - *Esophageal Neoplasms/genetics/pathology
MH  - Aldehyde Dehydrogenase, Mitochondrial/genetics
MH  - *Carcinoma, Squamous Cell/pathology
MH  - NF-E2-Related Factor 2/genetics
MH  - Claudin-4
MH  - Risk Factors
MH  - Ethanol
MH  - Acetaldehyde/metabolism
MH  - Carcinogenesis
MH  - RNA, Messenger
OTO - NOTNLM
OT  - NRF2 target genes
OT  - acetaldehyde
OT  - esophageal mucosa
OT  - esophageal squamous cell carcinoma
OT  - ethanol
EDAT- 2022/09/08 06:00
MHDA- 2022/10/29 06:00
CRDT- 2022/09/07 21:23
PHST- 2022/09/08 06:00 [pubmed]
PHST- 2022/10/29 06:00 [medline]
PHST- 2022/09/07 21:23 [entrez]
AID - 10.1620/tjem.2022.J077 [doi]
PST - ppublish
SO  - Tohoku J Exp Med. 2022 Oct 25;258(3):195-206. doi: 10.1620/tjem.2022.J077. Epub 
      2022 Sep 8.