To evaluate and project the disease burden of early-onset colorectal cancer (EOCRC), and to identify its major risk factors.

Data from the Global Burden of Disease Study 2021 were used. EOCRC was defined as colorectal cancer diagnosed at ages 15-49 years. We extracted the absolute numbers and crude rates of incidence, mortality, and disability-adjusted life years (DALYs) of EOCRC in the world, China, and the United States from 1990 to 2021. Age-standardized rates were then calculated accordingly, and the associated risk factors were summarized. Joinpoint regression was applied to assess temporal trends in global EOCRC age-standardized incidence rate (ASIR), mortality rate (ASMR), and DALY rate. The Bayesian age-period-cohort (BAPC) model was used to project the EOCRC burden from 2022 to 2040.

In 2021, an estimated 211 900 new EOCRC cases were reported globally, corresponding to an ASIR of 5.37 per 100 000, along with 79 500 deaths and a total of 4.00 million DALYs lost. China experienced a substantially higher burden than the global average, with an ASIR of 10.02 per 100 000, an ASMR of 3.11 per 100 000, and an age-standardized DALYs rate(ASDR) of 160.93 per 100 000, disproportionately affecting males. The United States had a higher ASIR(10.73 per 100 000) than China, but exhibited lower ASMR(2.53 per 100 000) and ASDR(127.81 per 100 000). From 1990 to 2021, ASIRs increased globally (AAPC=0.374) and more markedly in China (AAPC=1.423), whereas ASMR (AAPC=-0.855) and DALY rates (AAPC=-0.834) declined. In China, ASMR and DALY rates declined overall but rebounded in recent years, whereas in the United States, ASIR began to decrease after 2017, while ASMR and DALY rates remained relatively stable. By sex, China's male ASIR increased by 89.7% between 1990 and 2021, with rises also observed in ASMR and DALY rates in recent years. Regarding risk factors, insufficient whole-grain intake and excessive red meat consumption emerged as the leading modifiable contributors to EOCRC mortality and DALYs both globally and in the two countries, jointly accounting for 31.20% and 30.82% of the global burden, respectively. Heavy alcohol consumption and tobacco use were particularly significant contributors among Chinese men. Projections indicated that by 2040, China's ASIR is projected to rise to 17.04 per 100 000, indicating a continued increase in disease burden, whereas the United States is expected to maintain a downward trend.

Although China's EOCRC mortality and DALY burden have declined over the past three decades, the incidence remains markedly higher and is rising more rapidly compared with the global level and the U.S. More effective public health strategies are urgently needed, including promoting earlier and wider implementation of colorectal cancer screening, strengthening follow-up and referral systems, improving dietary structure, and intensifying tobacco and alcohol control, to mitigate the growing burden of EOCRC.