Modifiable risk factors contributing to the rising incidence of early-onset colorectal cancer in the United States over three decades: a Global Burden of Disease analysis

Introduction

Colorectal cancer (CRC) is a major cause of cancer-related morbidity and mortality worldwide. Globally, CRC accounts for approximately 1.9 million new cases and 935,000 deaths each year, ranking as the third most diagnosed cancer and the second leading cause of cancer-related death (1). In the United States (US), CRC similarly represents a substantial public health burden, with more than 150,000 new cases and over 50,000 deaths projected annually, despite long-standing advances in screening and prevention strategies (2).

Historically, CRC has been considered a disease of older adults, and screening programs have therefore focused on individuals aged 50 years and older. In recent years, however, early-onset colorectal cancer (EOCRC), defined as CRC diagnosed before the age of 50 years, has emerged as an important clinical and public health concern. EOCRC is particularly notable because it affects individuals outside the scope of traditional screening programs and occurs during early and mid-adulthood, with potential long-term clinical, psychosocial, and economic consequences. Observations from population-based studies in the US and Europe have raised concern that EOCRC may reflect differences in risk exposure across successive birth cohorts rather than screening practices alone (3,4).

Several lifestyle and metabolic factors have been implicated in EOCRC, including changes in diet quality, rising prevalence of obesity, and early-onset metabolic dysfunction, which have become more common across younger generations and have been linked to colorectal carcinogenesis in epidemiologic studies (5). As a result, the U.S. Preventive Services Task Force recommended lowering the CRC screening initiation age to 45 years from 50 years (6). However, despite expanding recommendations and increasing uptake, CRC screening rates remain heterogeneous across populations and continue to lag behind national target levels (7). Despite these observations, the quantitative contribution of modifiable dietary and metabolic risk factors to EOCRC-related mortality and disability burden at the national level remains incompletely characterized, particularly across extended time periods using consistent methodology (8-10).

In this study, a comprehensive longitudinal assessment was conducted to quantify the burden of EOCRC in the US from 1990 to 2023, including incidence, mortality, and disability-adjusted life years (DALYs), and evaluated the contribution of key dietary and metabolic risk factors using data from the Global Burden of Disease (GBD) study. We present this article in accordance with the GATHER reporting checklist (11) (available at https://jgo.amegroups.com/article/view/10.21037/jgo-2026-0314/rc).

Methods

Data source

The GBD database, developed by international health research collaborations (12), provides comprehensive estimates of disease, injury, and risk factor effects on health at national and global levels. Data on the age-specific incidence rate (ASIR), the age-specific mortality rate (ASMR), and the age-specific DALY rate (ASDR) of EOCRC in the US were obtained for both sexes between 1990 and 2023. The GBD defines CRC according to the International Classification of Diseases (ICD)-10 codes C18–21. GBD 2023 calculates the correlations between risk factors and diseases using a comparative risk evaluation method; in this study, only the most detailed risk factors are selected for presentation. All estimates are presented with 95% uncertainty intervals (UIs). Data were extracted from the Global Health Data Exchange (GHDx) and the GBD Results Tool (https://vizhub.healthdata.org/gbd-results), which provide open-access, publicly available estimates for download. Data were included for the US, both sexes, ages 15–49 years, for the years 1990–2023. No additional ad hoc exclusions were applied beyond the GBD study’s internal methodology. UIs for GBD estimates were generated using 1,000 draws from the posterior distribution of the modeled estimates, reflecting uncertainty from input data variability, model parameters, and covariate estimation. Uncertainty arising from the joinpoint regression model selection and projection assumptions was not formally quantified. Population estimates and age structures used for age-specific and 2050 projections were sourced from the GBD 2023 demographic inputs as provided through the IHME GBD framework. This study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments.

Statistical analysis

Trends in EOCRC incidence and mortality by sex and risk factor from 1990 to 2023 were analyzed using joinpoint regression. This method identifies time points (“joinpoints”) that segment the timeline into distinct linear trends based on minimizing mean square error. It is widely applied in studying temporal trends in infectious diseases, chronic illnesses, and cancers. Because tumor rates typically follow a Poisson distribution, a log-linear model was employed (11).

Models with four joinpoints (five-line segments) were uniformly applied to capture potential trend shifts and facilitate consistent comparisons. The joinpoint regression model fits a log-linear form: ln(y) = β₀ + β₁x + δ₁(x − τ₁)₊ + ε, where τ represents each joinpoint. Annual percent change (APC) and average annual percent change (AAPC) were derived from the fitted segments. The optimal number of joinpoints was determined using permutation testing (Monte Carlo method, 4,499 permutations) with a significance level of 0.05, and four joinpoints were consistently identified as the best fit. No formal sensitivity analysis was conducted; all estimates are reported with 95% UIs derived from the GBD modeling framework. Future projections to 2050 were performed using the GBD forecasting framework, which applies mixed-effects regression and autoregressive integrated moving average (ARIMA) models to extend historical disease trends (12). The reference scenario extrapolated observed trends forward without any assumed change in risk factor exposure, reflecting the expected burden under continuation of current dietary and metabolic patterns. Alternative future scenarios were constructed by replacing appropriate reference trajectories for risk factors with hypothetical trajectories of gradual elimination of risk factor exposure from current levels to 2050. Forecasting uncertainty was propagated from the underlying GBD modeling framework and is expressed as 95% UIs around all projected estimates (13). All analyses were conducted using Joinpoint Regression Software (version 4.9.1.0).

Results

Mortality attributed to risk factors

In 1990, the leading contributors to EOCRC-attributable mortality were a diet low in whole grains (17.8%), a diet high in red meat (16.2%), and a diet high in processed meat (13.8%) (Figure 1A). Alcohol use accounted for 13.6% of attributable deaths, followed by high body mass index (BMI; 11.5%) and diet low in milk (10.6%) (Figure 1A-1C). Smoking, high fasting plasma glucose, diet low in calcium, low physical activity, and diet low in fiber contributed smaller fractions ranging from 7.5% to 1.0% (Figure 1B-1D).

Figure 1 Trends in EOCRC death burden attributable to dietary, metabolic, and behavioral risk factors in the United States, 1990–2023 (both sexes), expressed as attributable death percentages. (A) Major dietary risks; (B) metabolic risks; (C) behavioral risks; (D) minor dietary risks. EOCRC, early-onset colorectal cancer.

By 2023, the pattern shifted substantially. A diet high in processed meat emerged as the leading contributor to EOCRC-attributable mortality (18.4%), overtaking a diet low in whole grains (17.7%) (Figure 1A). A diet high in red meat (16.4%) and high BMI (16.1%) ranked third and fourth, respectively, with the latter showing the largest absolute increase over the study period (+4.6%) (Figure 1A,1B). Alcohol use remained stable at 13.9%, while smoking declined to 5.2% (Figure 1C). High fasting plasma glucose nearly doubled from 3.7% to 6.6% (Figure 1B, Table 1).

Overall burden of EOCRC in the US

Mortality trends

The ASMR for EOCRC in the US showed a consistent upward trend from 1990 to 2023. The ASMR rose from 2.48 (95% UI: 2.31–2.69) to 3.00 (95% UI: 2.75–3.24). Males consistently had higher rates than females, increasing from 2.74 (95% UI: 2.47–2.99) to 3.37 (95% UI: 2.96–3.76), while females rose from 2.23 (95% UI: 2.01–2.52) to 2.62 (95% UI: 2.34–2.91) (Figure 2A, Table 2).

Figure 2 Trends in EOCRC burden in the United States, 1990–2023. (A) ASMR, (B) ASIR, (C) ASPR, and (D) ASDR, all per 100,000 population, stratified by sex (male, female, both). Shaded areas indicate 95% UI. ASDR, age-specific DALY rate; ASIR, age-specific incidence rate; ASMR, age-specific mortality rate; ASPR, age-specific prevalence rate; DALY, disability-adjusted life year; EOCRC, early-onset colorectal cancer; UI, uncertainty interval.

Incidence trends

The ASIR of EOCRC in the US showed a steep upward trend between 1990 and 2023. The ASIR rose 47.1% from 1990 to 2023, increasing from 8.01 (95% UI: 6.83–9.44) to 11.79 (95% UI: 9.89–13.61). Males consistently had higher rates than females, with the gap widening as male ASIR rose from 8.75 (95% UI: 7.45–10.32) to 13.10 (95% UI: 11.00–15.56), while females rose from 7.27 (95% UI: 6.01–8.72) to 10.44 (95% UI: 8.65–12.34) (Figure 2B).

Prevalence trends

The ASPR of EOCRC in the US increased substantially from 1990 to 2023, rising from 55.07 (95% UI: 45.58–66.59) to 83.58 (95% UI: 68.16–98.08). Males consistently showed higher prevalence than females; male ASPR rose from 59.98 (95% UI: 49.73–72.78) to 91.93 (95% UI: 74.31–110.56), while females rose from 50.15 (95% UI: 40.44–61.42) to 75.00 (95% UI: 61.25–91.05) (Figure 2C).

DALYs trends

The ASDR rates related to EOCRC continued to rise between 1990 and 2023. The ASDR rate rose from 125.41 (95% UI: 115.17–136.28) in 1990 to 150.82 (95% UI: 137.37–162.98) in 2023. Males consistently bore a higher burden; male ASDR rates increased from 138.48 (95% UI: 124.15–150.91) to 169.68 (95% UI: 148.21–190.93), while female rates rose from 112.28 (95% UI: 100.96–128.27) to 131.44 (95% UI: 116.76–145.92), reflecting a widening disparity (Figure 2D).

2050 projection

The 2050 projection shows that if the current reference trend continues, the ASMR will show a limited decline to 2.42 per 100,000 (95% UI: 1.8–3.16) by 2050. However, in a perfect scenario where key risk factors are effectively controlled, the projected burden will drop more than half to 1.14 per 100,000 (95% UI: 0.85–1.49) by 2050, indicating a markedly greater reduction compared with the reference scenario (Figure 3).

Figure 3 Projected EOCRC burden under reference and risk-reduction scenarios in the United States through 2050. Lines represent mean projections, with shaded areas indicating uncertainty intervals. EOCRC, early-onset colorectal cancer.

Discussion

This national analysis demonstrated that the burden of EOCRC in the US increased substantially between 1990 and 2023, with incidence and prevalence increasing by nearly 40–50%, while mortality and DALYs rose by approximately 15–20%, in parallel with population level changes in dietary, metabolic, and behavioral risk factors, concurrent with the emerging recognition of EOCRC as a distinct clinical and biological entity rather than simply an earlier presentation of late-onset disease. These trends showed that EOCRC is becoming increasingly common among younger adults, which is consistent with other national surveillance data showing that CRC has become the leading cause of cancer-related death among U.S. men younger than 50 years and the second leading cause among women in this age group (2).

Similar patterns in EOCRC incidence have been reported across Europe, with relative rises of approximately 20–30%, suggesting that this trend is not geographically isolated and likely reflects shared shifts in early-life exposures rather than region-specific factors (4). Collectively, these observations support the recognition of EOCRC as a distinct clinical and biological entity.

Risk-factor attribution analyses indicate that dietary and metabolic exposures were the dominant modifiable contributors to EOCRC mortality. In 1990, diet-related risks, particularly low whole-grain intake and high consumption of red and processed meat, accounted for a substantial proportion of EOCRC-attributable deaths. By 2023, a clear shift was observed, with processed meat consumption emerging as the leading dietary contributor. These findings are concordant with a meta-analysis that demonstrated that approximately 15–20% higher CRC risk associated with red and processed meat consumption (14). This association could be explained through pathways involving heme iron–mediated oxidative stress, formation of N-nitroso compounds, and carcinogen exposure during high-temperature cooking (15). Although dietary guideline recommendations from the NutriRECS consortium questioned the certainty of this association, these conclusions remain controversial and inconsistent with the broader epidemiologic and biologic evidence base (16). The growing contribution of diet-related risk factors observed in this analysis aligns with these findings and suggests that generational shifts toward energy-dense, highly processed diets may be central drivers of the rising EOCRC burden. Prospective cohort studies have shown that poorer diet quality and higher intake of ultraprocessed foods are associated with approximately 30–50% higher risk of CRC precursors in younger adults (17,18).

Metabolic dysfunction represents another major contributor to EOCRC mortality. High BMI accounted for an increasing share of EOCRC-attributable deaths over time, consistent with meta-analytic evidence demonstrating approximately 30% higher EOCRC risk among overweight individuals and nearly twofold higher risk among those with obesity (19). Importantly, evidence suggests that excess adiposity earlier in life confers greater relative risk than weight gain later in adulthood, highlighting the cumulative effects of prolonged metabolic exposure (20). In parallel, elevated fasting plasma glucose and diabetes contributed meaningfully to EOCRC mortality, consistent with studies reporting 20–30% higher EOCRC risk and dose–response relationships between blood glucose levels and CRC risk (20,21). In contrast, the relative contribution of some risk factors declined over time.

Smoking-related EOCRC mortality showed a gradual reduction, consistent with declining smoking prevalence in the US. Similarly, low milk intake accounted for a smaller proportion of EOCRC-attributable deaths, aligning with evidence suggesting modest protective effects of dairy and calcium intake (22,23). However, these favorable trends were outweighed by increasing exposure to obesity, metabolic syndrome, and adverse dietary patterns among younger cohorts.

In this analysis, the 2050 projection indicates that continuation of current trends would yield only modest reductions in EOCRC burden, whereas sustained modification of dietary and metabolic risk factors could produce substantially greater declines by 2050. The widening gap indicates the importance of sustained population-level interventions targeting metabolic health and diet, including early obesity and diabetes prevention, improved diet quality, and risk-adapted screening strategies for high-risk younger individuals (24,25).

This study has several strengths and limitations. The use of GBD data enabled age-specific estimation of EOCRC incidence, mortality, and DALYs over more than three decades, allowing robust evaluation of long-term trends. A key strength of this analysis is the integration of longitudinal burden estimates with formal risk-factor attribution, providing a comprehensive, population-level assessment of the magnitude and drivers of EOCRC burden beyond incidence alone and offering actionable insight into modifiable dietary and metabolic risk factors relevant to prevention and public health planning. Limitations include reliance on modeled estimates, inability to infer individual-level causality, lack of race- and ethnicity-specific analyses, which could identify any potential disparities. Finally, the absence of granular clinical and treatment data limited the ability to stratify this group of young population by disease stage and severity. As with all GBD analyses, estimates are subject to variability in the quality and completeness of underlying national surveillance data. Although US cancer registry coverage is high, potential underreporting of EOCRC in younger populations and inconsistency in diagnostic coding across time may introduce bias. Risk factor attribution estimates are based on modeled exposure-response relationships and comparative risk evaluation, which may not fully capture joint effects or confounding between co-occurring risk exposures.

In conclusion, EOCRC remains a significant and persistent public health burden in the US. This analysis shows that dietary and metabolic risk factors contribute substantially to EOCRC burden and that sustained population-level prevention could meaningfully reduce incidence, mortality, and disability by 2050, underscoring the need for early, targeted public health strategies beyond screening alone.

Conclusions

The burden of EOCRC in the US has risen substantially over three decades, driven by increasing exposure to modifiable dietary and metabolic risk factors. The emergence of processed meat consumption as the leading attributable contributor to EOCRC mortality, alongside the growing impact of high body-mass index and elevated fasting plasma glucose, highlights the central role of diet quality and metabolic health in colorectal carcinogenesis among younger adults. Projections to 2050 indicate that targeted elimination of these exposures could reduce EOCRC mortality by more than half compared to the reference trend. These findings underscore the need for upstream prevention strategies addressing dietary patterns and metabolic health early in life, extending public health efforts beyond age-based screening thresholds alone.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the GATHER reporting checklist. Available at https://jgo.amegroups.com/article/view/10.21037/jgo-2026-0314/rc

Peer Review File: Available at https://jgo.amegroups.com/article/view/10.21037/jgo-2026-0314/prf

Funding: The article processing charge (APC) was supported by New York Medical College as part of resident support.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jgo.amegroups.com/article/view/10.21037/jgo-2026-0314/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. This study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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