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. 2026 Jun 26;71(10):5071–5082. doi: 10.1007/s10620-026-10078-6

Disease Burden of Early-Onset Pancreatic Cancer in Adults Aged 20–54 Years in Low- and Middle-Income Countries: A GBD 2023 Analysis

Shan Zhuang 1,✉, Peihua Zhang 2, Yujie Feng 3
PMCID: PMC13558321  PMID: 42360575

Abstract

Background

Pancreatic cancer incidence rises in low- and middle-income countries (LMICs), yet data on early-onset disease (20–54 years) are scarce.

Methods

Using Global Burden of Disease Study 2023 data (1990–2023), we analyzed incidence, mortality, and disability-adjusted life years (DALYs) for early-onset pancreatic cancer in LMIC adults. Trends were assessed via estimated annual percentage change (EAPC), stratified by World Bank income groups. Decomposition analysis quantified epidemiological/demographic drivers. Socioeconomic inequalities were evaluated using socio-demographic index (SDI); projections to 2050 employed autoregressive integrated moving average models.

Results

From 1990 to 2023, LMIC early-onset pancreatic cancer cases and deaths increased by 125% and 128%, respectively. Age-standardized incidence (ASIR EAPC: 0.68%) and mortality rates rose. Lower-middle-income countries showed the steepest incidence surge (+ 282%; ASIR EAPC: 1.65%). Young women (20–34 years) in low/lower-middle-income countries bore higher burden, contrasting higher-income regions. Burden correlated positively with national income and exhibited an S-shaped SDI association. Epidemiological changes drove increases in lower-income settings. Socioeconomic inequalities widened; age-standardized rates are projected to rise through 2050.

Conclusion

Early-onset pancreatic cancer burden is escalating across LMICs, with distinct patterns by income level. Young women in lower-income settings are specifically vulnerable. Targeted prevention and resource allocation are urgently needed.

Supplementary Information

The online version contains supplementary material available at https://doi.org/10.1007/s10620-026-10078-6.

Keywords: Pancreatic cancer, Low- and middle-income countries, Early-onset cancer, Global Burden of Disease , Health equity

Introduction

Pancreatic cancer stands as one of the most aggressive and lethal malignancies globally [1]. This malignancy is characterized by insidious early symptoms and inherent resistance to conventional therapies, and its five-year survival rate remains below 10% worldwide [2, 3]. Despite advances in molecular biology and targeted therapy, these breakthroughs have not yet been translated into clinical survival benefits. Thus, the prevention and early identification of pancreatic cancer are paramount [4, 5]. Traditionally, pancreatic cancer has been viewed as more prevalent in high-income countries and among older populations, and this prevalence is linked to industrialized lifestyles [6, 7].

However, low- and middle-income countries (LMICs) are undergoing a profound epidemiological transition. Propelled by urbanization and globalization, LMICs are confronting a “double burden” of disease [8]. The relationship between economic development and health is complex. As measured by the socio-demographic index (SDI), economic growth in LMICs is often accompanied by the rapid emergence of carcinogenic risk factors—such as high-calorie diets and sedentary behaviors—at a rate faster than healthcare systems can adapt [9–11]. Consequently, the burden of cancer is rising in resource-constrained settings, yet research remains predominantly based on populations in higher-income countries. This causes significant knowledge gaps regarding local risk profiles and health inequities [12, 13]. It is necessary to investigate the nonlinear disease burden arising from these socioeconomic disparities [14–16].

The disease burden of early-onset pancreatic cancer in adults aged 20 to 54 years is particularly concerning within this shifting landscape [17, 18]. This trend is alarming, as these individuals are in their prime years of working and family-building. A lethal diagnosis at this life stage poses severe threats to macroeconomic stability and family welfare [19]. Furthermore, younger patients often present with distinct molecular and clinical characteristics compared to older cohorts [20]. Crucially, the burden of pancreatic cancer may not be distributed equally between sexes in developing regions. The age-specific trends and sex-based disparities should be analyzed in depth to uncover the unique epidemiological features driving this rise in LMICs.

Leveraging data from the Global Burden of Disease (GBD) Study 2023, the present research systematically analyzed the burden of pancreatic cancer among adults aged 20–54 across LMICs from 1990 to 2023. It aims to quantify key metrics of the burden, decompose the drivers of increasing rates, evaluate socioeconomic inequalities, and project future trends through 2050.

Methods

Data Source and Study Framework

This study is a secondary analysis based on publicly available data extracted from the GBD 2023, which is produced by the Institute for Health Metrics and Evaluation (IHME). The GBD 2023 provides a comprehensive, consistent, and comparable framework for global health assessment. It systematically integrates multisource data from censuses, vital registration systems, epidemiological surveillance, academic literature, and other sources. By applying sophisticated statistical modeling techniques such as DisMod-MR 2.1 and spatiotemporal Gaussian process regression, GBD provides annual estimates of health loss for 371 diseases and injuries across 204 countries and territories from 1990 onward. The complete methodological framework, data inputs, and modeling strategies of GBD have been published in detail elsewhere. Our analysis focused on pancreatic cancer (International Classification of Diseases, Tenth Revision [ICD-10] code C25). The study period was set from 1990 to 2023, the target population was strictly limited to adults aged 20 to 54 years, and the geographical scope encompassed all regions classified as LMICs per the fiscal year 2023 criteria of the World Bank.

Country Grouping and Socioeconomic Metrics

To assess the impact of socioeconomic status, LMICs were categorized into low-, lower-middle-, and upper-middle-income groups per the 2023 gross national income (GNI) criteria of the World Bank. Additionally, the SDI—a composite measure of income, education, and fertility ranging from 0 to 1—was employed to evaluate the association between overall development and disease burden.

Quantification of Disease Burden

Estimates for incidence, prevalence, mortality, disability-adjusted life years (DALYs), years of life lost (YLLs), and years lived with disability (YLDs) were extracted from the GBD database. Metrics were analyzed as absolute numbers and age-standardized rates (ASR) per 100,000 population, standardized using the GBD global reference population. All estimates were reported with 95% uncertainty intervals (UIs).

Quantification of Long-Term Trend

Temporal trends from 1990 to 2023 were quantified using the estimated annual percentage change (EAPC). This metric was derived from a log-linear regression model:

lnASR=α+β×calendaryear
EAPC=100×expβ-1

Decomposition of Burden Drivers

A decomposition analysis was conducted to partition the net change in incident cases and deaths into three drivers: population growth, population aging, and epidemiological changes. This method distinguished demographic effects from true changes in the risk of disease.

Assessment of Inequality and Future Projections

The socioeconomic disparities were analyzed using Pearson correlation coefficients for GNI and locally weighted regression smoothing (LOESS) for SDI. Inequalities of health were quantified using the concentration index (CI) and slope index of inequality (SII) for 1990 and 2023. Finally, burden trends through 2050 were projected using autoregressive integrated moving average (ARIMA) models. The ARIMA models were selected based on the Akaike information criterion.

Results

Overall Burden of Pancreatic Cancer in LMICs

Between 1990 and 2023, the absolute burden of pancreatic cancer among adults aged 20–54 in LMICs escalated substantially (Fig. 1, Table 1–2 and Table S1–S4). Incident cases grew by 125%, rising from 20,783 (95% UI 17,260–25,309) to 46,725 (95% UI 37,764–56,665), while the number of prevalent cases increased by 137%, from 23,300 (95% UI 19,268–28,326) to 55,184 (95% UI 44,606–66,827). Deaths increased by 128%, from 17,441 (95% UI 14,345–21,129) to 39,712 (95% UI 31,535–49,458). Consequently, overall health loss measured in DALYs surged by 121% to reach 1,726,480 (95% UI 1,375,824–2,149,357). This rise was overwhelmingly driven by premature mortality (YLLs increased by 121%), although the nonfatal component (YLDs) also exhibited a significant increase by 128%, reaching 10,876 (95% UI 7,227–15,170).

Fig. 1.

Fig. 1

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Trends in age-standardized rates of early-onset pancreatic cancer (EOPC) in adults aged 20–54 years in low- and middle-income countries (LMICs) and by gross national income (GNI) category, 1990–2023. A Incidence rates. B Prevalence rates. C Years lived with disability (YLDs). D Years of life lost (YLLs). E Disability-adjusted life years (DALYs). F Mortality rates

Table 1.

Incidence of early-onset pancreatic cancer (EOPC) in adults aged 20–54 years in low- and middle-income countries (LMICs), by gross national income (GNI) category, 1990 and 2023

Location Absolute incident cases (1990) Absolute incident cases (2023) Percentage change (PC) (%) Age-standardized incidence rate (ASIR) (1990) (per 100,000) ASIR (2023) (per 100,000) Estimated annual percentage change (EAPC) (%)
All LMICs 20,783.47 46,725.17 125 1.23 1.62 0.68
GNI-L 769.27 2677.21 248 0.97 1.23 0.66
GNI-LM 3059.68 11,702.95 282 0.48 0.86 1.65
GNI-UM 16,954.52 32,345.02 91 1.76 2.48 0.91
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Table 2.

Prevalence of early-onset pancreatic cancer (EOPC) in adults aged 20–54 years in low- and middle-income countries (LMICs), by gross national income (GNI) category, 1990 and 2023

Location Absolute prevalent cases (1990) Absolute prevalent cases (2023) Percentage change (PC) (%) Age-standardized prevalence rate (ASPR) (1990) (per 100,000) ASPR (2023) (per 100,000) Estimated annual percentage change (EAPC) (%)
All LMICs 23,300.36 55,183.85 137 1.38 1.91 0.83
GNI-L 860.92 3130.14 264 1.08 1.44 0.78
GNI-LM 3389.75 13,651.19 303 0.53 1.00 1.81
GNI-UM 19,049.69 38,402.51 102 1.98 2.94 1.06
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Even after adjusting for demographic shifts via age-standardization, a persistent upward trend remained evident. The age-standardized incidence rate (ASIR) increased from 1.23 (95% UI 1.02–1.50) per 100,000 in 1990 to 1.62 (95% UI 1.31–1.96) in 2023, with an EAPC of 0.68% (95% CI 0.59–0.78). Similarly, the age-standardized prevalence rate (ASPR) rose with an EAPC of 0.83% (95% CI 0.73–0.92), and the age-standardized death rate (ASDR) grew annually by 0.71% (95% CI 0.61–0.81). Statistically significant increases were also observed in standardized rates for DALYs, YLLs, and YLDs (EAPCs of 0.56%, 0.56%, and 0.72%, respectively). These findings confirmed that the escalating burden reflected a genuine increase in age-specific risk beyond population growth and aging.

GNI-Stratified Burden of Pancreatic Cancer

Stratification by GNI level revealed profound disparities in both distribution and temporal dynamics. Throughout the study period, upper-middle-income (GNI-UM) countries consistently bore the highest burden. In 2023, these nations showed the largest absolute numbers: 32,345 incident cases, 38,403 prevalent cases, 27,128 deaths, and 1,167,798 DALYs. They also exhibited the highest ASR, with an ASIR of 2.48 (95% UI 2.08–2.89) and an ASDR of 2.08 (95% UI 1.71–2.51) per 100,000. However, this group showed the most modest increase in proportion. The incidence and deaths grew by approximately 90% since 1990. Their standardized rates also rose at a comparatively slower pace. The recorded EAPC was 0.91% for ASIR (95% CI 0.79–1.03) and 0.90% for ASDR (95% CI 0.77–1.03).

Lower-middle-income (GNI-LM) countries had absolute numbers lower than those in GNI-UM nations in 2023. However, they had the most substantial relative increases: incident cases surged by 282%, prevalence by 303%, deaths by 302%, and DALYs by 297%. This rapid escalation was mirrored in their ASR, where GNI-LM countries exhibited the highest EAPCs among all income categories (ASIR: 1.65%, 95% CI 1.55–1.75; ASDR: 1.82%, 95% CI 1.70–1.94).

Despite having the lowest absolute burden and standardized rates, incident cases in low-income (GNI-L) countries increased by 248% and deaths by 275% from 1990 to 2023. However, the growth in their standardized rates was less pronounced than in GNI-LM countries (ASIR EAPC: 0.66%, 95% CI 0.32–1.00; ASDR EAPC: 0.87%, 95% CI 0.54–1.20). These findings highlighted a nonlinear relationship. While the highest burden resided in the wealthiest LMICs, the fastest escalation was seen in the GNI-LM nations. These results suggest an evolving public health crisis.

National Trends in Burden of Pancreatic Cancer

National-level data for 2023 indicated extreme heterogeneity (Figure S1). A greater than 57-fold difference in ASIR was noted between Ukraine (4.61, 95% UI 4.08–5.20) and Mozambique (0.08, 95% UI 0.05–0.10). This disparity was consistent across all metrics. Belarus exhibited the highest age-standardized prevalence (4.72, 95% UI 4.26–5.25), while Mozambique again recorded the lowest (0.08). The nonfatal burden (YLDs) ranged from 0.84 in Moldova to 0.02 in Mozambique, that is, a 42-fold difference.

Regarding premature mortality, Ukraine recorded the highest age-standardized YLL rate at 171.21 (95% UI 150.32–196.22), which contrasted sharply with 2.10 in Mozambique. Consequently, the overall health impact (DALYs) was most severe in Ukraine (171.21) and Belarus (146.68), representing an 81-fold difference compared to Mozambique (2.11). In terms of absolute volume, the burden was concentrated in populous nations. China accounted for the highest number of incident cases (17,320), deaths (14,619), and DALYs (623,038).

Temporal trends showed divergent trajectories (Figure S2). Several countries exhibited alarming increases in the burden of pancreatic cancer. Turkmenistan displayed the most rapid increase in ASIR (EAPC: 9.81%, 95% CI 8.30–11.35) and ASDR (EAPC: 9.87%, 95% CI 8.36–11.40). Cabo Verde had the highest annual growth in DALY rates (8.65%), and the ASIR in Vietnam increased by 4.79% annually. Conversely, a few countries showed a pattern distinct from the global trends. Swaziland (Eswatini) recorded the most substantial decrease (ASIR EAPC −2.42%), followed by Nigeria (−1.40%), Madagascar (−1.36%), and Rwanda (−1.16%). Argentina, Kazakhstan, and Turkey also showed slight but significant downward trends. The observed reductions indicated potential opportunities to identify protective factors.

Age and Sex Disparities in the Burden of Pancreatic Cancer

The burden of pancreatic cancer across LMICs displayed a clear pattern that reversed with age (Fig. 2). Among young adults (20–29 years), the burden in females was comparable to or exceeded that in males. However, this pattern reversed decisively around age 30. Thereafter, the burden in men surpassed that in women across all metrics, and the gap widened progressively with age. In the 50–54 age group, incidence (8.20 vs 4.24) and mortality rates (7.31 vs 3.71) in males were nearly double those in females, and DALYs reached 280.93 per 100,000 in males compared to 142.49 in females.

Fig. 2.

Fig. 2

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Sex ratios of age-standardized rates for early-onset pancreatic cancer (EOPC) in adults aged 20–54 years in low- and middle-income countries (LMICs) and by gross national income (GNI) category, 1990–2023. A Incidence rates. B Prevalence rates. C YLDs. D YLLs. E DALYs. F Mortality rates

Economic development strongly influenced these patterns. In GNI-UM countries, males bore a substantially higher burden than females across nearly all of adulthood, and the burden in men consistently doubled that in women in the 50–54 age group across all metrics (e.g., incidence: 10.59 vs 5.22; deaths: 9.36 vs 4.47). This suggested potent sex-specific risk factors in more developed economies.

In contrast, young women in GNI-LM and GNI-L countries had an excess burden. In GNI-LM countries, the prevalence rate in women aged 20–24 was 2.5 times that in men (0.10 vs 0.04). This was most extreme in GNI-L countries, where the higher burden in women extended across the age range of 20–34 years. Notably, among women aged 20–24 in GNI-L nations, the incidence rate was 2.4-fold higher than in men (0.12 vs 0.05), and YLDs were three times higher. This exceptionally high burden among young women in resource-limited settings should be investigated promptly.

Association Between Burden of Pancreatic Cancer and Economic Development

Correlation analysis demonstrated a significant positive relationship between GNI per capita and all six indicators of age-standardized burden (Fig. 3). However, smoothed regression analysis revealed a nonlinear, sigmoidal trajectory. The burden remained low in the poorest nations, accelerated sharply during the transition from low- to lower-middle-income statuses, and decelerated or plateaued in GNI-UM nations. This pattern suggested that the burden of pancreatic cancer was intricately linked to the epidemiological transition driven by socioeconomic development.

Fig. 3.

Fig. 3

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Association between gross national income (GNI) per capita and age-standardized rates of early-onset pancreatic cancer (EOPC) in adults aged 20–54 years in low- and middle-income countries (LMICs), 2023. A Incidence rates. B Prevalence rates. C YLDs. D YLLs. E DALYs. F Mortality rates

Decomposition Analysis for Drivers of the Burden of Pancreatic Cancer

Decomposition analysis identified distinct drivers across income categories (Fig. 4). In GNI-UM countries, the increase in the burden of pancreatic cancer was predominantly attributable to demographic factors. Population aging contributed 51.4%–63.3% of the rise, and population growth contributed a further 39.6%–46.2%. Critically, epidemiological changes (risk-adjusted rates) made a negative contribution across all metrics (ranging from −0.74 to −7.94%), indicating a decline in underlying age-specific risk.

Fig. 4.

Fig. 4

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Decomposition analysis of the drivers of absolute changes in the burden of early-onset pancreatic cancer (EOPC) in adults aged 20–54 years in low- and middle-income countries (LMICs) and by gross national income (GNI) category, 1990–2023. Contributions are shown for population growth, population aging, and changes in age-specific rates (epidemiological change). A Incidence. B Prevalence. C YLDs. D YLLs. E DALYs. F Deaths

Conversely, GNI-LM countries faced a “triple burden.” Population growth was the leading driver (> 50%), compounded by substantial adverse epidemiological shifts (36.2%–39.4%) and population aging (~ 9%–10%). In GNI-L countries, rapid population growth accounted for > 75% of the increase in the burden of pancreatic cancer. While aging had a negligible effect, epidemiological changes still accounted for 20.8%–25.5% of the rise. Thus, mechanisms differed fundamentally. Demographic transitions drove the rise in the burden of pancreatic cancer in GNI-UM countries, whereas GNI-LM and GNI-L nations faced the combined pressures of demographic change and a genuinely increasing risk of disease.

Widening Socioeconomic Inequalities

Socioeconomic inequalities worsened substantially between 1990 and 2023 (Fig. 5). The CI for all six metrics remained positive and increased markedly (e.g., CI rose from 0.255 to 0.422 for incidence and from 0.259 to 0.415 for deaths). This suggested that the burden became increasingly concentrated in higher-SDI countries.

Fig. 5.

Fig. 5

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Relative socioeconomic inequality (concentration index) in the burden of early-onset pancreatic cancer (EOPC) among adults aged 20–54 years in low- and middle-income countries (LMICs), stratified by socio-demographic index (SDI), 1990–2023. A Incidence. B Prevalence. C YLDs. D YLLs. E DALYs. F Deaths

Absolute inequality, measured by the SII, also surged (Fig. 6). The SII for crude incidence rates more than doubled from 0.97 (95% UI: 0.78–1.17) in 1990 to 2.15 (95% UI: 1.82–2.49) in 2023. Similarly, the gap in crude death rates widened from 0.82 to 1.79. These results confirmed that health inequities regarding pancreatic cancer consistently deepened, as evidenced by increases in both the CI and SII.

Fig. 6.

Fig. 6

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Absolute socioeconomic inequality (slope index of inequality) in the burden of early-onset pancreatic cancer (EOPC) among adults aged 20–54 years in low- and middle-income countries (LMICs), stratified by socio-demographic index (SDI), 1990–2023. A Crude incidence rates. B Crude prevalence rates. C Crude YLDs. D Crude YLLs. E Crude DALYs. F Crude death rates

Future Projections for Burden of Pancreatic Cancer

Projections of the ARIMA model indicated that current trends would continue and accelerate through 2050 (Figure S3). The age-standardized DALY rate was forecasted to climb from 59.71 (95% UI: 47.58–74.34) in 2023 to 70.51 (95% UI: 61.17–79.86) by 2050. Consistent increases were predicted across all indicators. ASIR was projected to rise to 1.91 (95% UI: 1.64–2.19), age-standardized prevalence to 2.34, and the age-standardized death rate to 1.59 (95% UI: 1.37–1.80). A progressively increasing challenge to public health was noted, and enhanced strategies of prevention and control were needed.

Discussion

This study presents the first comprehensive trend analysis of the burden of pancreatic cancer among adults aged 20–54 in LMICs. It reveals a rapidly escalating and profoundly inequitable public health crisis. Our analysis highlights four pivotal findings regarding the evolving epidemiology of this lethal malignancy. First, the absolute burden surged by over 120% across LMICs, and it was driven by a genuine increase in age-specific risk rather than demographic factors alone [21]. Second, the drivers of this escalation exhibited extreme heterogeneity. While GNI-UM countries were impacted largely by aging, lower-income nations faced a “triple threat” of population growth, aging, and a worsening profile of disease risk. Third, we identified a pronounced age-sex disparity in the disease burden, where the burden in young women significantly exceeded that in men in resource-limited settings. This pattern is completely distinct from that observed in wealthier nations. Finally, socioeconomic inequalities widened substantially over the past three decades. The burden became increasingly concentrated in higher-SDI regions, even as the absolute gap between high- and low-SDI countries expanded. These insights provide crucial evidence for formulating precise, context-specific prevention strategies.

The drivers fueling the growth of the burden of pancreatic cancer were found to be inconsistent across different income levels. In GNI-UM nations, the increase in the disease burden is almost entirely a result of the inexorable demographic factors of population growth and aging. In fact, the age-specific risk (epidemiological change) shows a downward trend. This may signal that these nations make progress in the control of risk factors, such as more effective tobacco control, broader health education, and improved management of metabolic conditions like diabetes. These efforts may have already begun to positively impact the risk of pancreatic cancer [22, 23]. In contrast, GNI-LM and GNI-L countries are experiencing rapid population growth and a marked increase in the risk of disease, both of which are driving the disease burden up. This dual impact indicates that these countries are in the midst of an epidemiological transition. On one hand, they have not fully overcome traditional health threats; on the other, risk factors associated with industrialized lifestyles—such as obesity, unhealthy diets, and physical inactivity—are proliferating at an unprecedented rate. The rapid rise of these risk factors has led to a surge in the incidence of metabolic syndrome and type 2 diabetes, both of which are potent established risk factors for pancreatic cancer [24–26]. The situation observed in GNI-LM countries, where population growth, aging, and worsening risk coexist, implies the most severe challenge for their health systems in future.

Through an in-depth analysis of the relationship between the socioeconomic disparities and disease burden, this study provides quantitative evidence for the “health transition” theory in pancreatic cancer. We observed a distinct S-shaped relationship between the burden of pancreatic cancer and the SDI. The burden is low in countries with the lowest SDI, accelerates sharply as the SDI increases, and finally plateaus at a high level in countries with a higher SDI. This is consistent with the global pattern of many noncommunicable diseases, where economic development disproportionately increases exposure to pathogenic risks during the initial stages [27]. More alarmingly, the calculations of the CI and SII demonstrate that socioeconomic inequality in the burden of pancreatic cancer has significantly worsened in both relative and absolute measures over the past three decades. This implies that the dividends of development have not led to equitable health and well-being. On the contrary, globalization and economic transition may have exacerbated the concentration of risk factors among vulnerable populations. Meanwhile, high-SDI countries have a greater capacity to respond to and mitigate these risks, which widens the health gap between affluent and poor nations [28, 29]. This finding is a grave warning for global health equity. It suggests that integrating the principle of health equity into all development policies is urgently needed.

Our research reveals that the sex disparity in the burden of early-onset pancreatic cancer reverses with age, and this pattern varies across socioeconomic levels. In GNI-UM countries, we observed a pattern consistent with traditional understanding, where the burden in men is markedly higher than that in women across almost all age groups. This is likely related to historical sex disparities in exposure to traditional risk factors such as smoking, alcohol consumption, and occupational exposures [30]. However, in GNI-L and GNI-LM countries, particularly among the youngest adults (ages 20–29), the burden of pancreatic cancer (especially incidence and prevalence) is significantly higher in women than in men. This phenomenon challenges our conventional understanding of the etiology of pancreatic cancer and strongly suggests the existence of underrecognized risk factors or susceptibility pathways specific to young women in resource-limited settings. Potential explanations include differences in genetic susceptibility across populations, exposure to specific regional environmental toxins (e.g., pesticides or heavy metals), indoor air pollution from cooking fumes, and unknown reproductive or hormonal factors [31, 32]. Furthermore, in settings with limited medical resources, we cannot rule out the possibility that young women may be more likely than young men to be diagnosed when seeking care for nonspecific symptoms like abdominal discomfort. Regardless of the cause, this finding urgently needs to be validated and explained through dedicated etiological research. Such research could open up entirely new avenues for primary prevention targeted at young women in these regions.

Previous global studies on the burden of pancreatic cancer have often focused on all age groups. In these studies, the conclusions are dominated by the large number of older patients, and the unsettling changes in younger populations are obscured. Although some studies have noted a rising incidence of early-onset pancreatic cancer in high-income countries [33], our research is the first to reveal substantial heterogeneity in the disease burden across LMICs. These countries comprise the vast majority of the global population. For instance, Eastern European countries like Ukraine and Belarus had the highest ASR among young adults in the present study, possibly due to higher rates of alcohol consumption and smoking in the region [34]. The EAPC in countries like Turkmenistan and Cabo Verde may reflect the extremely drastic socioeconomic and lifestyle changes in these nations in recent decades. In contrast, the declining trend in the burden of pancreatic cancer in a few countries, such as Eswatini and Nigeria, should be interpreted with caution due to the potential influence of data quality. However, it also provides valuable clues for exploring potential protective factors or successful public health interventions.

Although this study is based on the GBD, it also has inherent limitations. First, GBD estimates are based on statistical models of available data. The accuracy of these estimates is highly dependent on the quantity and quality of the primary data from each country. In many LMICs, especially GNI-L countries, high-quality cancer registries, vital statistics, and epidemiological surveillance data remain scarce. This data gap may lead to wider UIs for the estimates [35]. Second, this is an ecological study, and the associations it reveals are based on country-level aggregate data. The associations cannot be directly inferred as causal relationships at the individual level. For example, the association between SDI and the burden of pancreatic cancer does not directly prove a direct relationship between an individual’s income or education level and their risk of disease. Finally, the GBD data cannot provide detailed information on molecular subtypes of pancreatic cancer, tumor stage, genetic background, or individual risk factors (such as smoking, alcohol consumption, and diet). Thus, it is impossible to provide a deeper etiological explanation for the observed trends.

Despite these limitations, the findings have profound implications for public health and policy. First, health policymakers in LMICs must recognize that early-onset pancreatic cancer is no longer an issue predominantly related to high-income nations, but an immediate and worsening domestic health problem. Our predictive models show that age-standardized burden rates will continue to climb by 2050. This trend means that without decisive action, the health systems in LMICs will be under even greater pressure in future. Second, control strategies must be tailored to local conditions. For GNI-UM countries where the risk is declining but demographic pressures are immense, they should strengthen cancer screening, popularize early diagnostic techniques, and provide affordable, standardized treatment to cope with existing and new cases. For GNI-LM and GNI-L countries where the risk is rapidly escalating, they should place primary prevention at the core, vigorously promote tobacco control, healthy diets, and physical activity, and strengthen the management of diabetes and obesity [36]. Third, there is an urgent need to investigate the unique etiology behind the high risk of early-onset pancreatic cancer among young women in GNI-L regions. Fourth, addressing the widening health inequalities demands multisectoral action. Integrating health goals into policies on trade, agriculture, urban planning, and education is essential to reduce the social gradient of carcinogenic risks at their source.

Future research should be deepened in the following directions. First, high-quality, population-based prospective cohorts should be established in LMICs to collect individual-level data on risk factor exposure, which would enable researchers to more precisely identify the causes of early-onset pancreatic cancer. Second, international collaborative studies in genomic and molecular epidemiology should be conducted to compare the tumor molecular characteristics of patients from different regions, sexes, and age groups to explore whether unique pathogenic mechanisms exist. Third, health economic models should be used to evaluate the cost-effectiveness of various prevention and intervention measures (such as screening high-risk populations and promoting standardized chemotherapy regimens like FOLFIRINOX) at different resource levels to provide evidence for decision-making. Finally, case studies of countries with declining or stable burden trends should be strengthened to identify valuable experiences.

In summary, this research systematically analyzes the burden of pancreatic cancer among young and middle-aged adults in LMICs, revealing a concerning upward trend. This rising burden, which coincides with the socioeconomic development of these countries, exacerbates existing health inequalities. These findings suggest that coordinated global action is urgently needed. Effective responses must be grounded in evidence, tailored to local contexts, and centered on health equity. Only through such comprehensive strategies can the increasing burden of pancreatic cancer be mitigated and its potential to impede sustainable development averted.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 2583 KB) (2.5MB, docx)

Author Contributions

All authors contributed to the study conception and design. Writing—original draft preparation: Shan Zhuang; Writing—review and editing: Shan Zhuang and Peihua Zhang; Conceptualization: Shan Zhuang; Methodology: Shan Zhuang and Yujie Feng; Formal analysis and investigation: Shan Zhuang and Peihua Zhang; Resources: Shan Zhuang; Supervision: Shan Zhuang, and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript. Shan Zhuang is the guarantor of the article.

Funding

The authors declare that no funds, grants, or other support was received during the preparation of this manuscript.

Data Availability

The datasets analyzed during the current study are available in the Global Health Data Exchange (GHDx) repository: http://ghdx.healthdata.org/gbd-results-tool

Declarations

Conflict of interest

The authors declare no competing interests.

Ethics approval

Not applicable.

Consent to participate

Not applicable.

Consent to publish

Not applicable.

Footnotes

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Supplementary Materials

Supplementary file1 (DOCX 2583 KB) (2.5MB, docx)

Data Availability Statement

The datasets analyzed during the current study are available in the Global Health Data Exchange (GHDx) repository: http://ghdx.healthdata.org/gbd-results-tool

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