Global Cancer Etiology: Molecular Signatures, Therapeutic Disparities, and the role of Socio-economic Determinants

The global burden of cancer is increasingly shaped by socio-economic determinants that extend beyond geographic incidence patterns. While historically considered a disease of affluence, cancer now reflects a divergence between high-income countries (HICs) and low- and middle-income countries (LMICs), driven by distinct environmental, occupational, and structural exposures. This narrative review examines how socio-economic conditions act as primary determinants of cancer etiology by linking epidemiological trends to molecular evidence. A comprehensive literature search was conducted (2006-2026), focusing on cancer etiology, environmental carcinogenesis, mutational signatures, and health disparities. Three domains of socio-economic influence emerged from search. First, harmful exposures, including asbestos, aflatoxin B1, arsenic, heavy metals, and air pollution, are disproportionately concentrated in under-regulated populations. Second, these exposures produce distinct mutational signatures; aflatoxin-related hepatocellular carcinoma is associated with TP53 R249S and COSMIC Signature 24, while cancers in HICs often involve PI3K/AKT/mTOR pathway alterations. Third, disparities in screening infrastructure create "screening deserts," increasing mortality gaps. Socio-economic context fundamentally shapes cancer biology, incidence, and outcomes. Reducing disparities requires expanded genomic capacity in LMICs, targeted prevention strategies, and equitable access to precision oncology.