Update on the global, regional, and national burden of pancreatic cancer: Insights from the Global Burden of Disease 2021 Study

To the Editor: Pancreatic cancer (PC) is one of the most lethal malignancies, with a five-year survival rate below 10%. Despite advancements in treatment, PC is still associated with poor survival outcomes, contributing to a significant global disease burden.[1] In the context of global aging, a comprehensive report on the burden of PC is crucial to optimize healthcare resource allocation and formulate effective prevention strategies. Using the Global Burden of Disease (GBD) 2021 data, this study updated the incidence, mortality, and disability-adjusted life years (DALYs) for PC from 1990 to 2021 across 204 countries. Annual data, categorized by region, sex, and sociodemographic index (SDI) were obtained from the Global Health Data Exchange (GHDx) and supplemented with human development index (HDI) data. This study analyzed the estimated annual percentage change (EAPC) in the PC burden from 1990 to 2021, highlighting significant variations at global, regional, and national levels. In addition, we visualized the key risk factors contributing to PC mortality and DALYs. Globally, there were 508,533 new PC cases in 2021—2.45 times higher than that in 1990. The global age-standardized incidence rate (ASIR) and age-standardized mortality rate (ASMR) both increased, rising to 6.0 per 100,000, with a total of 505,752 deaths. DALYs surged by 117.2%, reaching 11.3 million [Figure 1A, Supplementary Figure 1, https://links.lww.com/CM9/C562]. The ASIR of PC increased gradually, with an EAPC of 0.34 (95% confidence interval [CI]: 0.31–0.36). Similarly, the ASMR exhibited an upward trend globally, reflected by an EAPC of 0.21 (95% CI: 0.18–0.23), underscoring persistent challenges despite advances in medical interventions [Supplementary Tables 1 and 2, https://links.lww.com/CM9/C562].Figure 1: Research diagram and summary of the study. (A) Global incidence, mortality, and DALYs cases and rates for pancreatic cancer (Bars correspond to the left Y-axis; lines to the right Y-axis). (B) The EAPC trends for ASDR, ASIR, and ASMR across global regions (1990–2021). (C) ASIR of pancreatic cancer in global and 21 regions by SDI, 1990–2021. (D) Correlation between EAPC and ASIR of pancreatic cancer in 1990; Correlation between EAPC and HDI in 2021. ASDR: Age-standardized DALY rate; ASIR: Age-standardized incidence rate; ASMR: Age-standardized mortality rate; DALYs: Disability-adjusted life years; EAPC: Estimated annual percentage change; HDI: Human development index; SDI: Sociodemographic index.At the regional level, there were significant variations in the EAPC across different SDI regions. The highest increases in both ASIR and ASMR occurred predominantly in low-to-middle SDI regions, with EAPCs of 1.57 (95% CI: 1.54–1.60) and 1.55 (95% CI: 1.52–1.58), respectively, indicating a rapidly escalating incidence and worsening mortality outcomes in settings with limited resources. The age-standardized DALY rate (ASDR) also revealed disparities, with low-to-middle SDI regions experiencing the highest growth (EAPC = 1.46, 95% CI: 1.39–1.49). For instance, Western Sub-Saharan Africa exhibited the most substantial growth (EAPC = 2.30, 95% CI: 2.04–2.38) [Figure 1B], highlighting the urgent need for targeted public health interventions in these high-burden countries [Supplementary Tables 1 and 2, https://links.lww.com/CM9/C562]. Nationally, disparities in the PC burden were pronounced. In 2021, the highest PC burden was observed in China, with 118,665 new cases (95% uncertainty interval [UI]: 94,623–144,663), 119,602 deaths (95% UI: 95,654–145,218), and 2,930,317 DALYs (95% UI: 2,301,049–3,575,079). Mongolia exhibited the highest national-level increase in ASIR (EAPC = 6.93, 95% CI: 6.16–7.71), followed by Turkmenistan and Cabo Verde, in which steep increases were observed. In contrast, some European nations, including Andorra and Sweden, demonstrated a slight decline. Similar discrepancies were observed in ASMR, with Egypt (EAPC = 3.77, 95% CI: 3.41–4.14) and Ghana (EAPC = 3.86, 95% CI: 3.69–4.04) experiencing rapid increases, reflecting challenges in treatment and healthcare access. Notably, Greenland recorded the highest ASIR, ASMR, and ASDR, highlighting its significant disease burden despite its high HDI. In addition, countries such as China, the United States, and Japan accounted for approximately half of the global PC burden, underscoring the burden of the disease in populous and economically influential nations [Supplementary Tables 1 and 2, https://links.lww.com/CM9/C562]. This study highlighted the socioeconomic disparities in PC burden, with high-SDI countries experiencing the highest incidence and mortality, driven by aging populations and metabolic risk factors. In contrast, low-to-middle SDI regions experienced the most rapid increase in incidence, due to insufficient healthcare resources, which further exacerbated mortality [Figure 1C, Supplementary Figures 2 and 3, https://links.lww.com/CM9/C562]. A key finding was the nonlinear relationship between EAPC and HDI, showing a positive association for countries with an HDI below 0.7 and a negative correlation above this threshold, reflecting differences in healthcare access, cancer awareness, and lifestyle factors [Figure 1D]. Our findings also revealed a sustained global rise in the PC burden from 1990 to 2021, with increasing age-standardized rates (ASRs) across sexes and regions. Men (53.8%, 273,617/508,533) exhibited a higher incidence than women (46.2%, 234,916/508,533), although the underlying causes remain unclear. The sharpest increases were observed in the low- and middle-income regions, where limited healthcare access and delayed diagnoses contributed to elevated mortality, underscoring the urgent need for improved healthcare infrastructure and resource allocation [Supplementary Figure 2, https://links.lww.com/CM9/C562]. Frontier analysis revealed a distinct pattern for PC compared to infectious diseases. Although socioeconomic improvements typically narrow the gap between actual and potential rates for infectious diseases, reducing their burden, PC follows the opposite trend. Higher SDI levels correlate with increased incidence and mortality, highlighting its unique epidemiology and disproportionate burden in more developed regions.[2] This study revealed a widening gap between actual and potential minimum PC incidence as SDI increased from 1990 to 2021. High-income regions, including North America, Western Europe, and the Asia-Pacific region, exhibited ASIRs that exceeded global averages. Notably, high-SDI countries such as Monaco, Finland, Japan, Germany, and Austria had the largest disparities, whereas low-SDI nations such as Somalia and Ethiopia had smaller gaps [Supplementary Figure 4, Supplementary Table 3, https://links.lww.com/CM9/C562]. These findings highlight the complex interplay between PC burden, socioeconomic status, and healthcare access, underscoring the need for tailored public health policies and equitable resource allocation. The key modifiable risk factors for PC mortality included high fasting plasma glucose levels (26.3%), tobacco use (14.0%), and high body mass index (BMI) (1.8%). Tobacco-related deaths were highest among men in Eastern Asia (28.2%) and Eastern Europe (25.0%), and among women in high-income North America (12.0%) and Western Europe (10.0%). Mortality due to hyperglycaemia was most pronounced in North Africa and the Middle East (men: 31.9%, women: 32.5%), whereas obesity-linked deaths peaked in high-income North America (men: 4.5%) and Eastern Europe (women: 5.1%) [Supplementary Figure 5, https://links.lww.com/CM9/C562]. These findings underscore the need for targeted interventions to address the modifiable risk factors globally. Dysregulated glucose metabolism in patients with diabetes or hyperglycaemia promotes PC development. Chronic hyperglycaemia promotes the formation of advanced glycation end products (AGEs), which activate the AGE-RAGE signalling pathway, driving chronic inflammation, oxidative stress, and DNA damage that facilitate tumour initiation and progression.[3] Given the increasing global prevalence of diabetes, hyperglycaemia-related mechanisms are likely to sustain high PC morbidity. Tobacco use remains another critical modifiable risk factor, with evidence indicating its direct carcinogenic effects, leading to increased mortality, particularly among male smokers. The pronounced sex disparity in smoking prevalence highlights the importance of targeted anti-smoking policies.[4] Furthermore, despite a recent decline in high BMI-associated PC deaths, obesity continues to substantially elevate cancer risk through adiposity-related inflammation, hormonal dysregulation, and metabolic disturbances.[5] Thus, interventions addressing glucose control, smoking cessation, and obesity prevention remain essential public health strategies for mitigating PC and improving global survival outcomes. Global ASRs for PC have steadily increased from 1990 to 2021, remaining persistently high and presenting a significant public health challenge worldwide. This study provides a comprehensive update on the epidemiological trends and key risk factors associated with PC, highlighting their positive correlations with SDI values, as well as the contributions of smoking, high BMI, and elevated blood glucose levels. Notably, the increasing burden in low- and middle-income regions warrants particular attention. These findings underscore the urgent need for tailored prevention strategies, enhanced medical resource allocation, and targeted public health interventions. Future research should focus on developing effective preventive measures and novel therapeutic approaches to reduce PC incidence, improve survival rates, and mitigate the global burden of this devastating disease. Funding This work was supported by grants from the Gansu Province Natural Science Foundation Project (No. 22JR5RA916), Lanzhou University First Hospital In-House Fund (No. ldyyyn2020-46), Science and Technology Development Plan Project of Lanzhou City (No. 2020-ZD-92), and Scientific Research Cultivation Program for Cuiying Scholars, Second Hospital of Lanzhou University (Nos. CYXZ2023-06 and CYXZ2023-08). Conflicts of interest None.