Early-onset colorectal cancer burden attributable to early-life obesity from 2000 to 2020 with projections to 2040

PURPOSE: Early-onset colorectal cancer (age <50 years) incidence has increased globally since the 1990s for unknown reasons. Early-life exposure to established risk factors like adiposity is suspected to play a role, but the contribution to the rising disease burden remains unknown. This study quantified the potential impact of rising early-life obesity on early-onset colorectal cancer in Australia. METHODS: Population attributable fractions for early-onset colorectal cancer were derived from meta-analytic relative risks and obesity prevalence estimates in adolescents (10-19-year-olds), using body mass index data for 1990-2022 from the Noncommunicable Diseases Risk Factor Collaboration. Under age-specific carcinogenesis latency assumptions, we linked adolescent obesity prevalence estimates to colorectal cancer incidence across age groups (20-29, 30-39, and 40-49 years) using observed cancer incidence data from Australian cancer registries covering 2000-2019 and age-period-cohort modelling to generate scenario-based estimates of incidence and obesity-attributable cases through 2040. Trends in obesity-attributable colorectal cancer incidence were quantified using joinpoint regression. RESULTS: The proportion of early-onset colorectal cancers attributable to adolescent obesity across 1990-2022 rose from 2% to 6% in men and 1-3% in women (average annual change: 3-4%). Although absolute attributable incidence rates were low, they increased 2-20% per year, varying by period, age-dependent lag, and sex. Under the projection assumptions applied, scenario estimates suggest that adolescent obesity could account for an estimated 1465 early-onset cases by 2040. CONCLUSION: Early-life obesity is estimated to account for a growing yet minor fraction of early-onset colorectal cancers in Australia and is therefore unlikely to be a major driver of the rising disease incidence. These findings suggest that childhood obesity prevention programs may have only a small public health impact on early-onset colorectal cancer prevention. Therefore, it is imperative that other causal risk factors - especially early-life exposures - are identified to inform prevention strategies that stem the rising disease burden.