Epidemiological risk factors and inferred p53 pathway dysregulation in Esophageal squamous cell carcinoma in the...

Esophageal squamous cell carcinoma (ESCC) is the most prevalent cancer in Somalia and constitutes a major public health concern in the Horn of Africa. Despite its high incidence, the molecular mechanisms underlying ESCC are not well characterized. This scoping review synthesizes published data on TP53 mutations, environmental and lifestyle risk factors, and the epidemiology of ESCC to identify knowledge gaps and guide future research.

The review was conducted in accordance with the PRISMA-ScR guideline and the Joanna Briggs Institute framework. A structured search was performed in PubMed, Scopus, Embase, and Google Scholar.

Twenty studies met the inclusion criteria. ESCC was consistently identified as the leading cancer, representing up to one-third of all malignancies in Somali and neighbouring populations, with most cases diagnosed at advanced stages. Molecular evidence was limited; no sequencing-based studies from Somalia were identified. However, immunohistochemical data indicated p53 overexpression in approximately 60-70% of ESCC cases, suggesting frequent TP53 pathway disruption. Regional studies reported TP53 mutation rates of 50-70%, lower than the 90% observed in high-incidence Asian populations. Key environmental exposures, including khat chewing, co-exposure to aflatoxin and fumonisin, biomass fuel smoke, polycyclic aromatic hydrocarbons, and consumption of very hot beverages, were strongly associated with increased ESCC risk.

This review demonstrates a substantial but poorly characterized burden of ESCC in the Horn of Africa, driven by distinct environmental and cultural exposures. Frequent TP53 pathway disruption is evident, yet genomic data remain scarce. Integrating exposure assessment with molecular profiling and enhancing food safety, clean cooking practices, and culturally tailored prevention strategies are essential to reduce ESCC incidence in the region.