Environmental determinants of leukemia and lymphoma: lessons from African epidemiology and global transition

Childhood leukemia and lymphoma display striking global heterogeneity that cannot be explained by genetic ancestry or diagnostic access alone. African populations, historically characterized by high infectious burden, nutritional stress, and poor sanitation, exhibit a markedly different spectrum of hematologic malignancies from high-income countries, including reduced incidence of common/pre-B acute lymphoblastic leukemia (c-ALL), absence of the early childhood ALL peak, and increased prevalence of Burkitt lymphoma and chloroma-associated acute myeloid leukemia. Drawing on African epidemiologic data and global comparative studies, this review examines how environmental factors across the life course-particularly maternal health, intrauterine exposures, early-life infection, immune programming, and socioeconomic transition-shape leukemogenic pathways. We place these observations in the context of contemporary models of leukemogenesis that recognize prenatal initiation of preleukemic clones with postnatal environmental modulation of disease progression. As low- and middle-income countries undergo rapid epidemiologic transition, understanding how improvements in sanitation, nutrition, and population mixing may alter leukemia incidence is increasingly relevant for prevention strategies. African experience thus provides a natural experiment for elucidating environmental contributions to leukemogenesis with implications extending well beyond the continent.