European Colonial Echoes in Cancer Risk: Lessons from the TP53 p.R337H Founder Variant in Brazil

Latin America's population is among the most genetically diverse in the world, shaped by centuries of European colonization, Indigenous American displacement, and forced African slave migration. This complex ancestry, combined with persistent social inequalities, influences cancer risk through both genetic and environmental factors. For example, Indigenous ancestry has been linked to a lower risk of breast cancer, a protective effect further influenced by reproductive patterns and access to healthcare. In this issue, Pinto and colleagues trace the history of the TP53 p.R337H founder variant, a mutation now present in about 1 in 300 people in southern Brazil. Their analysis shows that this variant was introduced during early Portuguese colonization and spread throughout Brazil as the population grew rapidly. This story highlights how historical events continue to shape cancer risk today. Founder mutations, such as TP53 p.R337H, are common across Latin America and often trace to Iberian ancestors. These variants offer unique opportunities for low-cost genetic screening and precision medicine, especially in regions with limited resources. They also serve as natural experiments for studying how genes and the environment interact to influence cancer risk. By understanding and leveraging these genetic legacies, we can enhance cancer prevention and treatment in Latin America, reduce disparities, and gain valuable insights to address global cancer health. See related article by Pinto et al., p. 210.