Sugar rationing during the first 1000 days and Early-Onset Cancer: A Natural Experiment.
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BACKGROUND: The "First 1000 Days" of life is a critical window for metabolic programming, while the long-term oncological consequences of nutritional exposures during this period remain understudied. We aimed to evaluate whether restricted sugar intake in utero and during early childhood reduces the risk of early-onset cancer diagnosis and mortality in adulthood, utilizing a natural experiment. METHODS: We analyzed 63,819 UK Biobank participants born between October 1951 and March 1956, spanning the end of UK sugar rationing (September 1953). Leveraging a quasi-experimental birth cohort design, we compared participants exposed to sugar rationing in utero and during infancy versus those unexposed. Early-onset cancer incidence (≤ 50 years) and mortality were ascertained via integrated national Cancer Registry and hospital inpatient records. Multivariable Cox proportional hazards models (including Gompertz distribution) were used to estimate hazard ratios (HRs), with exploratory site-specific analyses. RESULTS: Among 63,819 participants (56.3% female), 40,397 were exposed to rationing and 23,422 were unexposed. Early-life sugar restriction significantly reduced early-onset cancer risk [HR, 0.66 (0.53, 0.81); P < 0.001]. A dose-response relationship was observed, with peak protection in individuals exposed for up to 24 months postnatally. This protection was observed systemically across solid tumors, independent of specific cancer sites. Specificity was corroborated by null associations with negative controls (herpes zoster and cataract). No significant difference was found for cancer-specific mortality. CONCLUSIONS: Restricting sugar intake during the first 1000 days is associated with a reduced risk of early-onset cancer, extending the disease-free lifespan. The divergence between reduced incidence and unchanged mortality suggests early-life metabolic environments primarily influence tumor latency rather than biological aggressiveness. These findings highlight the potential long-term public health implications of early-life dietary guidelines against the rising burden of early-onset cancer.