Pancreatic cancer is one of the tumors with the poorest prognosis, often termed the "king of cancers." Its onset is insidious, and most patients are diagnosed at an advanced stage, lacking effective treatment options. The five-year survival rate is only about 4%(1, 2), According to the 2022 global cancer report, pancreatic cancer ranks as the 12th most common cancer but the 6th leading cause of cancer-related deaths (3)。In recent years, significant progress has been made in the diagnosis and treatment of many cancers, but effective treatments for pancreatic cancer remain limited, resulting in persistently high mortality rates. Numerous studies suggest that the incidence and disease burden of pancreatic cancer will continue to rise, especially in countries undergoing rapid demographic and epidemiological transitions(3–5)。Particularly in China, with industrial development, significant changes in diet structure, age structure, and environment have led to a continuous increase in cancer incidence, notably for pancreatic cancer(6, 7)。Therefore, a retrospective analysis of pancreatic cancer incidence in China over the past 30 years, coupled with projections of the future disease burden for the next 30 years, is necessary to formulate reasonable prevention and control strategies based on the national context.

The 2021 Global Burden of Disease, Injuries, and Risk Factors Study (GBD) database provides comprehensive and comparable data on the burden of pancreatic cancer, including many useful indicators recorded annually since 1990(8, 9)。In our study, we analyzed temporal changes in incidence, mortality, and Disability-Adjusted Life Years (DALYs), extracting trends for pancreatic cancer from 1990 to 2021. Furthermore, we projected the cancer burden up to 2050 to provide useful information for pancreatic cancer prevention and treatment in China.

3.1 From 1990 to 2021, the annual number of incident cases, deaths, and DALYs for pancreatic cancer in China increased. In 1990, these were 37,817.66 (31,791.43-44,068.33), 38,882.95 (32,790.26-45,259.84), and 1,120,352.88 (941,075.60-1,306,508.69), respectively. In 2021, the number of pancreatic cancer incident cases increased by 2.14 (1.27–3.19) times compared to 1990, deaths increased by 2.08 (1.22–3.10) times, and DALYs increased by 1.62 (0.87–2.52) times. However, after age standardization, the analysis of the disease burden showed a more moderate change, which could be explained by the accelerated aging of China's population.

Table 1

3.2 From 1990 to 2021, the trends in the pancreatic cancer burden in China by sex were similar, reflecting higher incidence, deaths, DALYs, and ASRs in 2021 (ASIR: 5.64 [4.52–6.84], ASMR: 5.72 [4.59–6.91], ASR of DALY: 137.23 [108.15-166.74]).In 2021, the incidence (46,385.85 [34,923.02-59,339.25]), deaths (47,443.04 [35,778.44-60,491.71]), DALYs (1,076,283.74 [806,635.69-1,392,991.84]), and ASRs (ASIR: 4.18 [3.15–5.34], ASMR: 4.29 [3.23–5.46], ASR of DALY: 154.94 [116.12-200.53]) for females were significantly lower than those for males, potentially related to poorer lifestyle habits among males [Fig. 1]。

ASIR: Age-Standardized Incidence Rate; ASMR: Age-Standardized Mortality Rate; DALY: Disability-Adjusted Life Year

3.3 According to the classification criteria based on patient age and gender, the chart analysis revealed that the incidence and mortality rates of male patients were higher than those of female patients, with the primary incidence concentrated between the ages of 55 and 80[Fig. 2]。

(a, b) Incident cases. (c, d) Deaths. (e, f) DALYs.

3.4 Changes in risk factors for pancreatic cancer mortality in China from 1990 to 2021 show that smoking decreased to the second leading cause, while high fasting plasma glucose became the primary risk factor. The primary risk factors for women and men, hyperglycemia and smoking, remained unchanged, indicating that the risk of disease burden caused by hyperglycemia was greater than that of smoking [Fig. 3]。

(a) incidence, (b) deaths, (c) Disability-Adjusted Life Years).

This study analyzed the disease burden of pancreatic cancer in China over the past 30 years and projected changes for the next 30 years. The research shows that between 1990 and 2021, the incidence, mortality, and DALYs of pancreatic cancer in China showed an upward trend, increasing by approximately two-fold, consistent with studies on pancreatic cancer in Europe and globally, but the growth rate was higher than in other countries(10–12)。After age standardization, the increasing trend was more moderate, which might be explained by China's population growth and severe aging. After grouping by sex, the incidence, mortality, and DALYs of pancreatic cancer were significantly higher in males than in females, attributed to poorer lifestyle habits and higher rates of smoking and alcohol consumption among males(13, 14), Analysis by age group indicated that the high-risk age for pancreatic cancer is between 55–80 years, due to declining pancreatic function, weakened cell self-repair capacity, and cumulative exposure to carcinogenic factors in older age, making gene mutations more likely(15–18)。These distribution patterns of pancreatic cancer in China are consistent with other related studies ,Therefore, pancreatic cancer prevention and control in China should focus on the middle-aged and elderly male population.(19–21)。

Analysis of risk factors for pancreatic cancer revealed that the primary risk factor shifted from smoking to high fasting plasma glucose, consistent with Wei's research (22)。This change is attributed to China's tobacco control policies and lifestyle changes leading to increased sugar intake. In the mechanism of pancreatic cancer induced by high blood glucose, exosomes and miR-19a become key mediators and effector molecules(23, 24), Furthermore, several potential driving mechanisms for PC cell proliferation and invasion include high glucose-activated p38 MAPK pathway activation, enhanced expression of GDNF and RET, induction of EGF expression, and EGFR transactivation(25–27)。Consequently, blood glucose control should be prioritized in subsequent pancreatic cancer diagnosis, treatment, and policy formulation, which could also reduce the incidence of other types of cancer. Due to the continuous growth of China's population, the absolute number of smokers has increased. Although currently the second leading causative factor, the disease burden attributable to smoking has still increased severalfold compared to 1990(28, 29)。The primary risk factors for women and men, hyperglycemia and smoking, remained unchanged, indicating that the risk of disease burden caused by hyperglycemia was greater than that of smoking.

Our BAPC prediction model shows an upward trend in the ASRs of the pancreatic cancer disease burden, projected to continue over the next 30 years. The balanced trend from 1990–2021 might be due to the offsetting of negative factors from aging and lifestyle changes by positive factors like health education, early screening, and medical advances. However, in the next 30 years, due to the lack of effective treatments, the high lethality of pancreatic cancer, and the continuous increase in risk factors such as high blood glucose, smoking, and obesity, the ASRs of the pancreatic cancer disease burden are projected to rise(6, 30, 31)。

Limitations of this study include, first, potential variations in patient data collection due to the large time span and differences in healthcare levels and policy investments across periods, potentially leading to higher clinical data collection volumes in recent years. Additionally, during the COVID-19 pandemic, some high-risk individuals for pancreatic cancer may have died prematurely, so the prediction model might overestimate the actual situation. However, this study's strengths lie in its large-scale and standardized data source, along with the establishment of a robust prediction model considering the effects of age, period, and birth cohort, lending high credibility to its conclusions. Hyperlipidemia and elevated body weight are significant contributors to the incidence and mortality rates of pancreatic cancer. Obesity is associated with chronic inflammation and insulin resistance. Adipose tissue, particularly visceral fat, secretes inflammatory mediators that can cause long-term DNA damage in cells. Furthermore, individuals with obesity frequently exhibit hyperinsulinemia; insulin itself promotes cellular proliferation and may expedite tumor progression(32–34). Research indicates that these factors can adversely affect postoperative survival rates in patients with pancreatic cancer.

Our study found that over the past three decades, the incidence, mortality, and number of DALYs for pancreatic cancer in China have shown an upward trend. Although the trend is more moderate after age standardization, considering the ongoing intensification of population aging in China, the actual disease burden of pancreatic cancer in the next 30 years might be higher than projected in this study. Furthermore, high fasting plasma glucose is the leading risk factor for pancreatic cancer, and onset is concentrated in the population aged 55 and above. Therefore, policy formulation should focus on regular screening for patients over 55 and prioritize blood glucose control in the population. These measures can help health systems better address this significant public health problem.