Increased reproductive cancer risks following early-life dichlorodiphenyltrichloroethane (DDT) exposure: Evidence from a historical population-based study in Taiwan (1952-1957).

Dichlorodiphenyltrichloroethane (DDT) was extensively applied for malaria control in Taiwan between 1952 and 1957, resulting in widespread early-life exposure. Limited evidence suggests that exposure to DDT during critical developmental windows may increase the risk of endocrine-related malignancies in adulthood. To investigate this association, we conducted a left-truncated cohort study utilizing Taiwan's National Health Insurance Research Database (NHIRD), including 2,327,099 individuals born during the DDT-based malaria eradication campaign. DDT exposure levels were estimated from historical indoor residual spraying records and categorized into six groups based on township-level spraying frequency (0-5 times). Kaplan-Meier survival analysis and Cox proportional hazards models were applied to estimate the association between early-life DDT exposure and the cumulative incidence of reproductive cancers. Over a 22-year follow-up (2000-2022), 81,592 reproductive cancer cases were identified. Each additional episode of township-level DDT spraying was significantly associated with an elevated cancer risk (aHR: 1.04, 95 % CI: 1.03-1.04 in women; aHR: 1.05, 95 % CI: 1.03-1.07 in men). Among women, breast (aHR: 1.04, 95 % CI:1.03-1.05), corpus uteri (aHR: 1.03, 95 % CI:1.01-1.05), and ovarian cancers (aHR: 1.06, 95 % CI:1.02-1.09) showed the strongest associations. In men, prostate cancer demonstrated the highest risk (aHR: 1.05, 95 % CI:1.03-1.07). A significant dose-response trend was observed (p < 0.0001). This historical exposure setting, grounded in a unique context and a nationwide database, provides epidemiologic evidence on the potential association between early-life DDT exposure and long-term carcinogenic risk. The findings contribute to the limited body of evidence from Asia and underscore the need for long-term surveillance in countries where DDT spraying is still ongoing.