Short Description Of Molecular Pathogenesis Of Gastric Cancer..pdf

This editorial article provides an overview of the molecular pathogenesis of gastric cancer (GC), highlighting key risk factors and recent advancements in understanding its genetic and epigenetic underpinnings.

Key Points:

- Global Impact: GC is the fifth most common cancer worldwide, with higher incidence rates in South America, East Asia, and Eastern Europe.

- Risk Factors: Important risk factors include Helicobacter pylori infection, smoked/fried food, low fruit and vegetable intake, high salt intake, geographical location, genetic predisposition, age, and sex (with men at higher risk).

- Hereditary Forms: Approximately 10% of GC patients show familial aggregation, with hereditary diffuse type gastric cancer, familial intestinal gastric cancer, and gastric adenocarcinoma with proximal polyposis being distinct forms.

- Molecular Subtypes: Genome-wide analyses have identified four molecularly distinct GC subtypes: Epstein-Barr virus-positive (EBV+), Micro Satellite Instable (MSI), genomically stable, and chromosomal unstable (CIN). MSI and EBV+ subtypes are clinically relevant.

- Pathogenesis Mechanisms:

- CIN: Characterized by aneuploidy, LOH, and translocations.
- MSI: Resulting from DNA replication errors leading to high frequency of mutations.
- Epigenetic Changes: Mutational activation/amplification of oncogenes, inactivation of tumor suppressor genes, altered cell-adhesion molecules, and dysregulation of growth factors and cytokines.

- Helicobacter pylori Contribution: CagA protein, encoded by the cytotoxin-associated gene A (CagA) pathogenicity island, plays a role in GC development by promoting proliferation, invasion, angiogenesis, and inhibiting apoptosis.

- Environmental Factors: Reactive Oxygen Species (ROS) from ingested food, smoke, and H. pylori infection contribute to decreased apoptosis and increased proliferation, potentially favoring carcinogenesis.