Abstract
An increase in incidence among young adults (generally those under the age of 50) has been reported for multiple cancer types, with colorectal cancer being among the most prominent.1 These trends are worrying, because they could indicate the emergence of new cancer risk factors at younger ages, with important implications for prevention and early detection among populations at risk. A shift in cancer demographics is a cause for concern because it could translate into an increasing cancer incidence among older adults as the younger cohorts age. Alternative explanations for an increasing incidence in young adults must also be considered: an increase in incidence because of improved methods of detection, changing criteria of disease classification that include borderline benign cases, increased uptake in screening, or greater awareness of symptoms leading to earlier or more frequent examinations. Such changes in cancer care or diagnostic artifacts could inflate incidence at younger ages that either would have been clinically undetected or would not have been diagnosed until later in life. Crucially, these artifactual explanations would not be expected to predict a corresponding rise in mortality. It is precisely for this reason that mortality trends serve as the most robust test of whether changing incidence in young adults reflects a genuine shift in disease risk. For all of these reasons, the contribution from Sung et al.2 on mortality trends in colorectal cancer across 49 countries is of particular interest. Using World Health Organization (WHO) mortality data from 1990 to 2023, supplemented by US national mortality data, the authors examined age-standardized colorectal cancer mortality trends among adults aged 25 to 49 years and compared them with adults aged 50 to 79 years across 49 countries. Their main finding was that among adults aged 25 to 49 years, colorectal cancer mortality increased in 18 of 49 countries during the most recent decade, decreased in 15, and remained stable in the remainder. The steepest increases of an average annual percentage change of 3% or more below age 50 were observed in several South American countries, including Paraguay, Uruguay, and Chile, as well as the United Kingdom. These countries demonstrated either more modest increases in mortality above age 50 (Paraguay and Chile) or evidence of decreasing mortality (Uruguay and the UK). Other large countries including Canada, the United States, and Australia, which have recently been the focus of attention on early-onset colorectal cancer, all showed a more modest increase in mortality at ages 25 to 49 of between 1% and 2% per year, alongside decreases at older ages. This divergence of rising mortality in younger adults occurring against a backdrop of stable or declining mortality among older adults is not a statistical curiosity. It is an epidemiological signal, and one that strongly suggests younger generations are experiencing a genuine elevated and worsening risk of colorectal cancer, driven by exposures or risk factor profiles distinct from those of earlier cohorts. An immediate conclusion from these results is that the increase in incidence of early-onset colorectal cancer is unlikely to be explained as an artifact of improved registration, better detection, or changing diagnostic criteria that include more benign forms of disease.2 These phenomena would not be expected to affect disease mortality. These results therefore reinforce the conclusion that the epidemiology of colorectal cancer is changing, and that efforts must be prioritized to understand why. The results do, however, paint a heterogeneous picture of evolving mortality trends. The presence of multiple South American countries among those with the highest rates of increase at ages 25 to 49 suggests that efforts to understand the epidemiology of early-onset colorectal cancer must include a sustained research focus in these countries. In much of Latin America, rising mortality among younger adults mirrors parallel increases among older adults, which points to a systemic challenge in cancer control infrastructure rather than a cohort-specific biological phenomenon. The rapid translation of rising incidence into death in these settings likely reflects limited access to early detection and treatment, underscoring the stark inequities that persist in global cancer care. Implementation of population screening and access of young adults to screening is globally heterogenous.3 Any research focus on colorectal cancer among young adults should not, therefore, distract from primary and secondary prevention efforts at older ages, nor from the urgent need to strengthen diagnostic and treatment capacity across the full age range in resource-limited settings. The results also observed no apparent mortality increase in 31 countries, primarily from Europe and East Asia. Of these countries with a stable or decreasing annual percentage change among adults aged 25 to 49, cancer incidence data from the IARC GLOBOCAN website are available from 18 of these countries over a similar period, and the data indicate an increase in incidence for the majority of them (Figure 1). This is also not a reason for complacency, given the time lag between increases in cancer mortality and those for cancer incidence that were previously reported in a similar group of countries by the same investigators.4,5,6 Estimated annual percentage change (EAPC, solid diamond) in age-standardized incidence rates (ASR, World standard population) per 100 000 population for colorectal cancer among individuals aged 25 to 49 years in countries with reported stable or decreasing mortality. Horizontal whiskers represent 95% confidence intervals. The vertical reference line at EAPC = 0 indicates no change. Estimates with confidence intervals entirely right or left of zero indicate significant increasing or decreasing EAPC, respectively. Countries marked with an asterisk (*) represent subnational data. The figure was generated using the Global Cancer Observatory, Cancer Over Time database and visualization tool (International Agency for Research on Cancer, World Health Organization). Data accessed on June 23, 2026 at https://gco.iarc.who.int/overtime. Data version: Version 2.1. These trends in colorectal cancer mortality confirm that the increasing incidence observed in many countries is real. Increasing incidence suggests that colorectal cancer mortality at ages 25 to 49 could be expected to increase in many of these countries in the forthcoming decades. Particularly worth monitoring are those countries, including Austria, Lithuania, New Zealand, the Netherlands, France, and Czechia, where prior declines in mortality among younger adults appear to be plateauing or reversing, even as mortality among older adults continues to fall. The results do not in themselves provide clues as to the underlying etiology. The authors mention that emerging evidence implicates metabolic health-related factors; however, the current evidence does not yet allow any single etiological pathway to be elevated above others. Formal birth cohort analyses of mortality trends, which the authors call for, will be essential to characterizing when and where inflection points in risk occurred and to informing targeted preventive strategies. Future studies will need to encompass a broad range of hypotheses, employ study designs that enable accurate identification of mutagenic and promotional risk factors, and specifically include those populations, particularly in Latin America and the Caribbean, where the increases in both incidence and mortality are the most striking. The international research community should treat the findings of Sung et al. as a call to action. The clinical implications of these findings require particular emphasis. These results indicate that it is important and urgent to raise awareness of early-onset colorectal cancer (CRC) among primary care providers and that young patients presenting with persistent lower gastrointestinal symptoms are evaluated with appropriate clinical vigilance. Population screening can detect precancerous lesions and cancers earlier, potentially reducing mortality; however, as the authors rightly warn, the benefits of population screening are context-sensitive. In many resource-limited settings, expanding screening coverage is only valuable within a health-care infrastructure that can respond to its findings. The study is not without limitations. The authors acknowledge potential misclassification of CRC deaths, the inclusion of appendiceal and anal cancers deaths in some countries, underrepresentation of low-income regions (particularly Africa and sub-Saharan Asia), and imprecision of estimates in smaller populations. It was not possible to adjust for heterogeneity of stage at diagnosis, access to treatment and care, or population screening infrastructure. Subgroup analyses by CRC subsite could not be conducted without introducing additional misclassification bias, a methodologically appropriate decision. Despite these constraints, the breadth of geographic coverage and the rigor of the joinpoint regression methodology provide a robust foundation for the conclusions drawn. The rise of CRC among young adults is no longer an emerging signal—it is an established trend in a growing number of countries, and mortality data now confirm that lives are being lost. The challenge ahead is threefold: to better understand the biological and environmental drivers of early-onset disease; to ensure that health-care systems recognize and respond to it promptly; and to develop context-appropriate strategies for prevention, early diagnosis, and treatment. The funder had no role in the writing of this editorial. Aedin Culhane (Writing—original draft, Writing—review & editing), Noor Kherreh (Writing—original draft, Writing—review & editing), and Paul Brennan (Writing—original draft, Writing—review & editing) No new data were generated or analyzed for this editorial. No funding was used for this editorial. Where authors are identified as personnel of the International Agency for Research on Cancer/World Health Organization, the authors alone are responsible for the views expressed in this article and they do not necessarily represent the decisions, policy, or views of the International Agency for Research on Cancer/World Health Organization.