Abstract
BACKGROUND: The global burden of colorectal cancer (CRC) has been steadily rising. However, a key knowledge gap persists regarding the HBMI-attributable burden in early-onset (EOCRC) versus late-onset (LOCRC) cases. The temporal patterns, geographic heterogeneity, and comparative trends remain poorly characterized, as prior studies often lack stratification by age of onset and detailed analysis across socio-demographic strata. OBJECTIVE: This investigation seeks to systematically quantify the burden of EOCRC and LOCRC attributable to HBMI at global, regional, and national levels from 1990 to 2021 and provides projections of the burden through 2040. METHODS: Epidemiological data, including number and rate for EOCRC and LOCRC were obtained from the Global Burden of Disease Study (GBD) 2021. Direct standardization method was employed to standardize rates across age-specific groups. The estimated annual percentage change (EAPC) model was utilized to analyze temporal trends from 1990 to 2021 across various countries, genders, SDI and GBD regions. Additionally, Nordpred and Bayesian age-period-cohort (BAPC) models were employed to forecast the burden of EOCRC and LOCRC owing to HBMI through 2040, both in terms of numbers and age-standardized rate (ASR). RESULTS: In 2021, HBMI was responsible for 359,538 disability-adjusted life years (DALYs) and 7,255 deaths in EOCRC, as well as 2,005,125 DALYs and 92,013 deaths in LOCRC. From 1990 to 2021, there was an increase of 130.97% in DALYs and 130.24% in deaths associated with EOCRC, while LOCRC saw rises of 133.32% and 139.71%, respectively. The global age-standardized DALYs rate (ASDR) and age-standardized mortality rate (ASMR) both exhibited an upward trend in EOCRC, regardless of gender. Conversely, in LOCRC, the global ASDR remained stable, while the ASMR exhibited a slight decline, a trend that was more evident in females. A declining trend was noted specifically among females in high-middle socio-demographic index (SDI) regions for EOCRC, and across both genders in high SDI regions combine females in high-middle SDI regions for LOCRC, the remaining SDI regions demonstrated varying degrees of upward trends in both ASDR and ASMR. Among GBD regions, High-income North America had the highest ASDR and ASMR for EOCRC, while Central Europe recorded the highest ASDR and ASMR for LOCRC. In contrast, East Asia reported the highest number of DALYs and deaths for both EOCRC and LOCRC. Furthermore, a nonlinear relationship was observed between the ASR and SDI in GBD regions for both EOCRC and LOCRC attributable to HBMI. Projections based on Nordpred and BAPC models revealed a consistent global increase in DALYs, deaths, ASDR, and ASMR for both EOCRC and LOCRC. CONCLUSION: From 1990 to 2021, the global burden of LOCRC attributable to HBMI remains significantly high and consistently exceeds that of EOCRC, but the rapid growth of EOCRC should be emphasized. The burden of CRC is closely associated with the SDI. While LOCRC has begun to decline in high-SDI regions, EOCRC continues to increase across all SDI regions. Over the next 20 years, the burden caused by EOCRC and LOCRC is expected to continue increasing.