Lymphocyte Micronucleus Formation Is Driven by Inflammation-Induced Oxidative DNA Damage in Oesophageal Cancer...

Area of Science:

• Genetics
• Oncology
• Molecular Biology

Background:

• Gastro-oesophageal reflux disease (GORD), Barrett's oesophagus (BO), and oesophageal adenocarcinoma (OAC) represent a disease spectrum.
• Understanding the mechanisms of DNA damage is crucial for early detection and treatment.

Purpose of the Study:

• To investigate the mechanisms of circulating DNA damage across the GORD, BO, and OAC spectrum.
• To assess the utility of lymphocyte micronucleus frequency (MN%) as a biomarker.

Main Methods:

• Quantified MN frequency in lymphocytes from healthy volunteers (HVs), GORD, BO, and OAC patients.
• Assessed plasma biomarkers of inflammation and oxidative stress.
• Performed ex vivo lymphocyte challenge assays and correlated tissue NF-κB expression with MN levels.

Main Results:

• OAC patients showed significantly elevated MN% compared to HVs, GORD, and BO patients.
• OAC lymphocytes exhibited increased sensitivity to vinblastine.
• Higher baseline MN% correlated with altered oxidative stress responses and was associated with specific plasma biomarkers and reduced oesophageal tissue IκB.

Conclusions:

• Systemic aneugenic and oxidative stress processes contribute to lymphocyte MN formation in OAC.
• MN% may be a minimally invasive indicator of inflammation-linked genomic instability in OAC.
• Further research is needed to determine the relevance of MN% to OAC progression.