Burden landscape of hepatobiliary and pancreatic cancers in Chinese young adults: 30 years’ overview and forecasted trends

Abstract

BACKGROUND

Hepatobiliary and pancreatic (HBP) cancers impose a considerable burden on young populations (aged 15 to 49 years), resulting in a substantial number of new cases and fatalities each year. In young populations, the HBP cancers shows extensive variance worldwide and the updated data in China is lacking.

AIM

To investigate the current status, trends, projections, and underlying risk factors of HBP cancers among young populations in China.

METHODS

The Global Burden of Disease Study 2019 provided data on the annual incidence, mortality, disability-adjusted life years (DALYs), age-standardized incidence rate (ASIR), mortality rate (ASMR), and DALYs rate (ASDR) of HBP cancers in young Chinese adults between 1990 and 2019. Temporal trends were assessed using estimated annual percentage change and hierarchical clustering. Sex-specific mortality and DALYs caused by various risks were analyzed across China and other regions, with future trends until 2035 projected using the Bayesian age-period-cohort model.

RESULTS

From 1990 to 2019, incident cases, deaths, DALYs, ASIR, ASMR, and ASDR for liver cancer (LC) in young Chinese individuals decreased, classified into 'significant decrease' group. Conversely, cases of gallbladder and biliary tract cancer and pancreatic cancer rose, categorized as either 'significant increase' or 'minor increase' groups. The contribution of risk factors to mortality and DALYs for HBP tumors increased to varying degrees. Healthy lifestyle behaviors, such as tobacco control, weight management, alcohol moderation, and drug avoidance, could lower HBP cancers incidence. Moreover, except for LC in females, which is likely to initially decline slightly and then rise, the forecasting model predicted that the ASIR and ASMR for all HPB cancers subtypes by gender will increase among young adults.

CONCLUSION

HBP cancers burden among young adults in China is expected to increase until 2035, necessitating lifestyle interventions and targeted treatment strategies to mitigate the public health impact of these cancers.

Key Words: Hepatobiliary and pancreatic cancers; Burden landscape; Young adults; Projection; China

Core Tip: The landscape of hepatobiliary and pancreatic (HBP) cancers among young adults (aged 15 to 49 years) in China was characterized by an overall increasing trend in addition to a substantial burden. This highlighted the persistently high prevalence of HBP malignancies. In general, adopting healthy lifestyle habits such as practicing tobacco control, maintaining a healthy weight, reducing alcohol consumption, and avoiding drug use could help decrease the risk of developing HBP cancers. These findings offered a comprehensive perspective for guiding healthcare approaches focused on primary prevention for Chinese youth.

INTRODUCTION

Gastrointestinal (GI) cancers are among the most devastating malignancies worldwide, accounting for over a quarter of all cancer cases and more than a third of cancer-related deaths[1]. Hepatobiliary and pancreatic (HBP) cancers, which include liver cancer (LC), gallbladder and biliary tract cancer (GBTC), and pancreatic cancer (PC), are lethal types of GI cancers[2]. China has a high morbidity and mortality rate from HBP cancers, with nearly 517500 new cases and 447300 deaths in 2022[3]. Notably, the prevalence of HBP cancers varies greatly across regions[4]. The burden of GI cancers is higher in rural areas than in cities, implying that specific assessments of the overall cancer spectrum in different socioeconomic settings are required for the development of effective prevention and control measures[5,6]. Moreover, China is expected to reach a population peak of 1.5 billion by 2030[7]. Combined with the demographic changes, China's cancer prevention and control continue to face significant challenges.

HBP cancers significantly impair patients' quality of life and life expectancy, particularly among young adults. Young cancer patients are more prone to experience long-term adverse outcomes, such as organ dysfunction, psychological distress, secondary malignancies, and high costs, potentially exacerbating disparities in access to anti-tumor strategies[8]. Additionally, patients with HBP cancers typically have limited treatment options and are refractory to most currently available anti-cancer therapies[9-11]. Emerging evidence shows that the incidence rate of GI cancers in the young is on the rise in recent years[12-14]. The cancer burden in this age group also exhibits distinct features, varying across risk factors, clinicopathologic variables, and survival prognosis, thereby complicating the preventive, screening, and therapeutic strategies[13,15,16], which should be considered in the development of health policy. However, compared to other age groups in China, the burden and trends of HBP cancers’ incidence and mortality in young adults remain unclear.

HBP cancers are expected to continue imposing a massive cancer burden in China, with far-reaching implications for society[17]. To inform public health policies and guide preventive and therapeutic programs, this study provided a comprehensive description of the HBP cancers burden among young adults in China over 30 years (1990-2019), stratified by gender, along with long-term trends in HBP cancers incidence and mortality until 2035.

MATERIALS AND METHODS

Data sources

The data on HPB cancers patients aged 15 to 49 spanning from 1990 to 2019 were acquired from the Global Health Data Exchange (GHDx) query tool, released by the Institute for Health Metrics and Evaluation, and accessible at https://ghdx.healthdata.org/gbd-2019. Indicators of data included annual incidence, mortality, DALYs, age-standardized incidence rates (ASIR), age-standardized mortality rates (ASMR), and age-standardized DALYs rates (ASDR) pertaining to HBP cancers by gender (both sexes, male and female) and age (from 15 to 49 years at 5-year intervals). These metrics were estimated by GBD study utilizing the Bayesian meta-regression tool DisMod-MR 2.1[18]. Population data spanning from 1990 to 2019 were sourced from the publicly available repository (https://ghdx.healthdata.org/record/ihme-data/gbd-2019-population-estimates-1950-2019). Projections for demographic trends for the interval 2020-2035 were derived from the publicly accessible database (https://ghdx.healthdata.org/record/ihme-data/global-population-forecasts-2017-2100). The socio-demographic index (SDI), utilized as a metric for assessing a nation's socio-demographic advancement, was categorized into five classes: < 0.46 as low, 0.46-0.60 as low-middle, 0.61-0.69 as middle, 0.70-0.81 as high-middle, and > 0.81 as high SDI[19]. In addition, regions were also segmented by World Bank income Categorization, classifying them as high-, upper-middle, lower-middle, and low-income ones. Employing a hierarchical clustering method, the estimated annual percentage change (EAPC) in morbidity and mortality rates across various nations were categorized. Subsequently, clusters of countries exhibiting analogous EAPC trajectories were identified. Furthermore, in assessing risk factor exposure, mortality, and DALYs attributable to these risks were also measured. Detailed methodologies of GBD study estimation have been elucidated elsewhere[20,21].

Statistical analysis

The EAPC is commonly employed for conveying trends in the age-standardized rate (ASR) over defined temporal intervals. This entails the application of regression analysis, where a line is fitted to the natural logarithm of the rate, expressed as y = α + βx + ε, with y representing ln (ASR) and x denoting the calendar year. The EAPC in ASIR, ASMR, and ASDR of HBP cancers among young adults in China was characterized as 100 × (e^β-1). The trends in ASIR, ASMR, and ASDR were expressed by EAPC value and its 95%CI.

The trends of ASIR and ASMR from 2020 to 2035 were predicted using the Bayesian Age Period Cohort (BAPC)[22]. All data were analyzed in R software (version 4.3.3). The predictive models utilizing BAPC incorporated software packages including "Nordpred (version 1.1)," "BAPC (version 0.0.36)," and "INLA (version 24.03.24)." All P values below 0.05 were considered statistically significant.

RESULTS

Burden of HBP cancers among Chinese young adults in 2019

In 2019, the estimated number of newly diagnosed LC cases among young adults was 44399, corresponding to ASIR of 10.40 and 1.69 per 100000 in males and females, respectively, with the ratio having significantly increased to 6.15 (Table 1). There were 33735 LC-related deaths, which roughly equaled the number of incidences, and nearly 87% of these cases were male patients (Table 2). In 2019, the DALYs and ASDR of LC in the young population reached a staggering 1598257 and 221.76, respectively (Table 3). As shown in Figure 1A-C, among different age cohorts, males had higher ASIR, ASMR, and ASDR than females in 2019. Additionally, all three age-standardized rates of LC increased across age groups in the young population.

Figure 1 Age-and gender-related age-standardized incidence rates, age-standardized mortality rates and age-standardized disability-adjusted life years rates of hepatobiliary and pancreatic cancers in young population of China in 2019. A: The age-standardized incidence rates (ASIR) of liver cancer (LC); B: The age-standardized mortality rates (ASMR) of LC; C: The age-standardized disability-adjusted life years rates (ASDR) of LC; D: The ASIR of the gallbladder and biliary tract cancer (GBTC); E: The ASMR of GBTC; F: The ASDR of GBTC; G: The ASIR of pancreatic cancer (PC); H: The ASMR of PC; I: The ASDR of PC.

Table 1 The incidence numbers and age-standardized incidence rate of primary liver cancer, gallbladder and biliary tract cancer and pancreatic cancer in 1990 and 2019 and their temporal trends from 1990 to 2019.

Characteristics	1990		2019		1990-2019
	Numbers	ASIR per 100000	Numbers	ASIR per 100000	EAPC (95%CI)
Liver cancer
Both	68811.36	10.29	44399.27	6.16	-3.51 (-4.44, -2.57)
Male	55050.88	15.94	38449.92	10.40	-3.10 (-4.01, -2.18)
Female	13760.48	4.26	5949.34	1.69	-5.27 (-6.25, -4.28)
Gallbladder and biliary tract cancer
Both	1821.08	0.27	3027.00	0.42	1.88 (1.69, 2.06)
Male	1007.66	0.29	1908.18	0.52	2.76 (2.42, 3.11)
Female	813.42	0.25	1118.83	0.32	0.72 (0.44, 1.00)
Pancreatic cancer
Both	4207.14	0.63	10997.43	1.53	3.26 (3.08, 3.43)
Male	2765.73	0.80	8085.22	2.19	4.06 (3.82, 4.31)
Female	1441.40	0.45	2912.20	0.83	1.59 (1.20, 1.97)

ASIR: Age-standardized incidence rate; EAPC: Estimated average percentage change.

Table 2 The mortality numbers and age-standardized mortality rate of primary liver cancer, gallbladder and biliary tract cancer and pancreatic cancer in 1990 and 2019 and their temporal trends from 1990 to 2019.

Characteristics	1990		2019		1990-2019
	Numbers	ASMR per 100000	Numbers	ASMR per 100000	EAPC (95%CI)
Liver cancer
Both	62017.77	9.28	33735.15	4.68	-4.09 (-5.03, -3.15)
Male	49755.43	14.40	29235.06	7.91	-3.72 (-4.63, -2.81)
Female	12262.34	3.80	4500.08	1.28	-5.68 (-6.70, -4.65)
Gallbladder and biliary tract cancer
Both	1477.00	0.22	2154.66	0.30	1.41 (1.22, 1.60)
Male	819.84	0.24	1385.09	0.37	2.36 (2.02, 2.71)
Female	657.16	0.20	769.57	0.22	0.12 (-0.18, 0.42)
Pancreatic cancer
Both	3769.90	0.56	9809.53	1.36	3.26 (3.08, 3.44)
Male	2490.14	0.72	7253.48	1.96	4.06 (3.81, 4.31)
Female	1279.75	0.40	2556.05	0.73	1.56 (1.18, 1.94)

ASMR: Age-standardized mortality rate; EAPC: Estimated average percentage change.

Table 3 The disability-adjusted life years numbers and age-standardized disability-adjusted life years rate of primary liver cancer, gallbladder and biliary tract cancer and pancreatic cancer in 1990 and 2019 and their temporal trends from 1990 to 2019.

Characteristics	1990		2019		1990-2019
	Numbers	ASDR per 100 000	Numbers	ASDR per 100 000	EAPC (95%CI)
Liver cancer
Both	3022653.23	452.18	1598256.61	221.76	-4.20 (-5.12, -3.27)
Male	2417358.23	699.80	1384244.50	374.50	-3.82 (-4.71, -2.93)
Female	605295.00	187.38	214012.11	60.95	-5.83 (-6.84, -4.80)
Gallbladder and biliary tract cancer
Both	72354.41	10.82	100846.97	13.99	1.21 (1.03, 1.38)
Male	40283.60	11.66	65189.56	17.64	2.17 (1.83, 2.51)
Female	32070.81	9.93	35657.41	10.16	-0.10 (-0.40, 0.20)
Pancreatic cancer
Both	184481.52	27.60	457701.30	63.51	3.04 (2.88, 3.21)
Male	121551.46	35.19	338968.44	91.71	3.86 (3.63, 4.10)
Female	62930.05	19.48	118732.87	33.82	1.32 (0.94, 1.70)

ASDR: Age-standardized disability-adjusted life years rate; EAPC: Estimated average percentage change.

In terms of GBTC, there were 3027 newly diagnosed cases among the young Chinese population, with 1908 cases among males and 1119 cases among females. The male/female ratio of ASIR reached 1.63 (Table 1). Furthermore, there were 2155 fatalities attributable to cancer among the young Chinese population, nearly equivalent to two-thirds of the incident cases (Table 2). The ASDR reached 65190 in young males and 35657 in young females (Table 3). Notably, across all age periods, ASIR, ASMR, and ASDR in males were far higher to those in females (Figure 1D-F), indicating an increased trend with age.

The number of new PC cases among young adult males was 8085, accounting for approximately 74% of patients. The male/female ratio of ASIR has grown slightly to 2.64 (Table 1). Additionally, there were 9810 PC-associated deaths in 2019, approaching the number of incident cases, which highlighted the high fatality of PC (Table 2). In 2019, the DALYs and ASDR of PC were 457701 and 63.51, respectively (Table 3). Intriguingly, akin to the findings in LC, the ASIR, ASMR, and ASDR of young males exhibited notable elevations, compared to those of young females (Figure 1G-I). The peaks in ASIR, ASMR, and ASDR in PC subgroups by gender closely resembled those observed in GBTC.

Trends of HBP cancers from 1990 to 2019

As shown in Table 1, the ASIR of LC in young Chinese adults decreased drastically from 1990 to 2019 (EAPC = -3.51; 95%CI: -4.44 to -2.57), especially from 1997 to 2004 (Figure 2A). Both gender groups manifested a steep downward trend, with the ASIR for females (EAPC = -5.27; 95%CI: -6.25 to -4.28) decreasing faster than that for males (EAPC = -3.10; 95%CI: -4.01 to -2.18; Table 1 and Figure 2A). Moreover, there was a notable concurrence in the decrement of the ASMR of LC with its ASIR over this period, exhibiting a substantial decline (EAPC = -4.09; 95%CI: -5.03 to -3.15; Table 2). The ASMR exhibited a decrease among both young male and female cohorts, with a slightly faster downward trajectory observed in females (Figure 2B). Remarkably, the ASDR showed an overall decline from 1990 to 2019 and exhibited a downward trend close to that of ASIR and ASMR (EAPC = -4.20; 95%CI: -5.12 to -3.27; Table 3 and Figure 2C). A stratified cluster analysis was conducted across 17 countries and regions by gender. Chinese young patients with LC were designated to the ‘significant decrease’ group, alongside regions such as World Bank upper-middle income, western Pacific, middle SDI, Global, and high-middle SDI (Figure 3A and B).

Figure 2 The age-standardized incidence rates, age-standardized mortality rates and age-standardized disability-adjusted life years rates of young patients with hepatobiliary and pancreatic cancers from 1990 to 2019. A: The age-standardized incidence rates (ASIR) of liver cancer (LC); B: The age-standardized mortality rates (ASMR) of LC; C: The age-standardized disability-adjusted life years rates (ASDR) of LC; D: The ASIR of the gallbladder and biliary tract cancer (GBTC); E: The ASMR of GBTC; F: The ASDR of GBTC; G: The ASIR of pancreatic cancer (PC); H: The ASMR of PC; I: The ASDR of PC.

Figure 3 Cluster analysis of hepatobiliary and pancreatic cancers based on estimated average percentage change data combining age-standardized incidence rates and age-standardized mortality rates across 17 countries and regions. A: Cluster analysis of liver cancer (LC) in males; B: Cluster analysis of LC in females; C: Cluster analysis of gallbladder and biliary tract cancer (GBTC) in males; D: Cluster analysis of GBTC in females; E: Cluster analysis of pancreatic cancer (PC) in males; F: Cluster analysis of PC in females. SDI: Socio-demographic index.

Contrary to LC, GBTC’s ASIR in China displayed a consistent upward trend spanning the years 1990 to 2019 (EAPC = 1.88; 95%CI: 1.69-2.06) (Table 1). This pattern especially has been observed from 1997 to 2004 (Figure 2D). In young patients, the males’ ASIR showed a more pronounced increase (EAPC = 2.76; 95%CI: 2.42-3.11) contrasted with females (EAPC = 0.72; 95%CI: 0.44-1.00). During this period, the ASMR generally rose (EAPC = 1.41; 95%CI: 1.22-1.60). Among males, the ASMR increased at a rate twenty times faster than that among females (males, EAPC = 2.36; 95%CI: 2.02-2.71; females, EAPC = 0.12; 95%CI: -0.18 to 0.42) (Table 2; Figure 2E). Furthermore, the ASDR for males demonstrated a significant upward incline (EAPC = 2.17; 95%CI: 1.83-2.51), whereas a declining trend was evident among females (EAPC = -0.10; 95%CI: -0.40 to 0.20) (Table 3 and Figure 2F). Stratified cluster analysis indicated that young males in China constituted the 'significant increase' group, highlighting the rapid rise in both ASMR and ASDR of GBTC (Figure 3C). In contrast, Chinese young females were categorized into the 'minor increase' group along with regions of middle SDI, low SDI, World Bank upper-middle income, and Global (Figure 3D).

From 1990 to 2019, there was a continuous rise in the ASIR of PC (EAPC = 3.26; 95%CI: 3.08-3.43) (Table 1). Among males, the ASIR manifested a more obvious upward trend (EAPC = 4.06; 95%CI: 3.82-4.31) (Table 2 and Figure 2G). Moreover, both ASMR (EAPC = 3.26; 95%CI: 3.08-3.44) and ASDR (EAPC = 3.04; 95%CI: 2.88-3.21) for PC showed a consistently advancing trend similar to the ASIR during the period. Both of them elevated in males and females, with a more drastic rising shift in males (Table 2 and Table 3, Figure 2H and I). In light of global patterns, young individuals with PC in China were classified into the 'significant increase' group, similar to regions such as World Bank upper-middle income, middle SDI, and western Pacific (Figure 3E and F).

Risk factors for HBP cancers

We extracted 87 risk factors on the GHDx website and found 5 risk factors associated with LC: Smoking, high alcohol use, high body mass index (BMI), drug use, and high fasting plasma glucose. We found a slight overall increase, except for males with high BMI and females with drug use. The proportion of deaths and DALYs caused by high BMI in males increased by 7.5%, while drug use in females increased by 5.6% and 5.5%, respectively (Figure 4 and Supplementary Figure 1). In China and other regions, smoking had a greater impact on deaths and DALYs in young males, whereas drug use contributed significantly more to young females (Figure 4). Nevertheless, on a global scale, elevated levels of fasting plasma glucose had a negligible effect on LC. Our analysis revealed that middle and high-middle SDI countries, World Bank upper-middle income countries, the east Mediterranean region, and the west Pacific region experienced a significant impact of smoking among males. However, drug use among females affected most regions. It is worth mentioning that in certain areas, such as high SDI and World Bank high-income countries, there is a significant association between high alcohol consumption and high BMI with hepatoma in young patients, following the same pattern as in China (Figure 4). This suggests that lifestyle intervention should be taken seriously as a preventive measure for young individuals. Overall, the pattern of mortality and DALYs caused by risk factors for LC in China is similar to that of countries with a moderate SDI and upper-middle income according to the World Bank, rather than high-income nations (Figure 4).

Figure 4 Proportion of liver cancer disability-adjusted life years and mortality in young adults attributable to risk factors across global, China, and other 15 regions in 2019. A: Risk factors of liver cancer (LC) in males; B: Risk factors of LC in females. DALYs: Disability-adjusted life years.

Our analysis revealed that the only risk factor associated with GBTC is a high BMI. The majority of GBTC-related deaths and DALYs in 2019 were high BMI, which was nearly twice as high as it was in 1990 (Figure 5 and Supplementary Figure 2). Furthermore, in the young population, high BMI exhibited a greater proportion of deaths and DALYs in females (14.6% and 14.4%) compared to that in males (7.7% and 7.7%) (Figure 5). We compared high BMI in China across different regions, revealing that the pattern of attributable risk proportion more closely aligned with countries defined as low-middle SDI and World Bank low-middle income, within western Pacific (Figure 5).

Figure 5 Proportion of gallbladder and biliary tract cancer disability-adjusted life years and mortality in young adults attributable to risk factors across global, China, and other 15 regions in 2019. A: Risk factors of gallbladder and biliary tract cancer (GBTC) in males; B: Risk factors of GBTC in females. DALYs: Disability-adjusted life years.

There were three primary risk factors for young patients with PC identified from 87 risk factors: Smoking, high fasting plasma glucose, and high BMI. Compared to the attributable risk factors in 1990, these three risk factors experienced a slight increase in their impact on deaths and DALYs in 2019 (Figure 6 and Supplementary Figure 3). While smoking represented the most significant risk factor in males (19.7% in deaths and 18.8% in DALYs), high BMI played a more important role in females (4.4% in deaths and 4.3% in DALYs) (Figure 6). Globally, these three factors were all related to higher deaths and DALYs of PC. There was a similarity in the cause profile of young PC patients across China, middle SDI, World Bank upper-middle-income nations, and a nearly identical proportion structure to western Pacific (Figure 6).

Figure 6 Proportion of pancreatic cancer disability-adjusted life years and mortality in young adults attributable to risk factors across global, China, and other 15 regions in 2019. A: Risk factors of pancreatic cancer (PC) in males; B: Risk factors of PC in females. DALYs: Disability-adjusted life years.

Predictions of HBP cancers burden from 2020 to 2035

Our projections showed that the ASIR and ASMR of LC among the young male cohort would continue to rise gradually from 2020 to 2035 (19.65/100000 in ASIR, 15.07/100000 in ASMR) (Figure 7A and B). Conversely, for young females, both the ASIR and ASMR were expected to remain stable until 2027 (1.75/100000 in ASIR, 1.11/100000 in ASMR), after which they would begin to rebound (2.54/100000 in ASIR, 1.69/100000 in ASMR) (Figure 7C and D). Additionally, our analysis suggested that for both sexes, the ASIR and ASMR of GBTC were expected to increase from 2020 to 2035 (Males: 0.83/100000 in ASIR, 0.53/100000 in ASMR; Females: 0.52/100000 in ASIR, 0.31/100000 in ASMR) (Figure 7E-H). Our findings also indicated a substantial increase for both ASIR and ASMR of PC in all young subgroups by gender yet more markedly for males during the same timeframe (males: 5.05/100000 in ASIR, 4.40/100000 in ASMR; females: 1.96/100000 in ASIR, 1.69/100000 in ASMR), aligning with the upward trajectory noted between 1990 and 2019 (Figure 7I-L). Altogether, the patterns of ASMR closely followed those of ASIR due to the high lethality of HBP cancers.

Figure 7 Trends in age-standardized incidence rate and age-standardized mortality rate for hepatobiliary and pancreatic cancers by gender in Chinese young adults from 1990 to 2035. A: The age-standardized incidence rate (ASIR) among male liver cancer (LC) patients; B: The age-standardized mortality rate (ASMR) among male LC patients; C: The ASIR among female LC patients; D: The ASMR among female LC patients; E: The ASIR among male gallbladder and biliary tract cancer (GBTC) patients; F: The ASMR among male GBTC patients; G: The ASIR among female GBTC patients; H: The ASMR among female GBTC patients; I: The ASIR among male pancreatic cancer (PC) patients; J: The ASMR among male PC patients; K: The ASIR among female PC patients; L: The ASMR among female PC patients.

DISCUSSION

HBP cancers are highly aggressive cancers that pose a significant threat to young populations worldwide, with high rates of morbidity and mortality[23-25]. It is crucial to increase awareness of these cancers and take proactive measures to reduce their substantial impact. The complex array of risk factors contributes to varying incidences of HBP cancers[17], complicating prevention efforts. Improving understanding of the various burdens these cancers cause will enhance the effectiveness of cancer prevention and treatment strategies for young adults. For instance, the routine hepatitis B (HBV) vaccination program recommended by the Chinese government significantly reduced HBV infection rates, leading to a decrease in LC incidence in the general population[26,27]. China and other countries bear a considerable burden of HBP cancers due to its poor prognosis[28-30]. Undoubtedly, the burden imposed by young adults stands out and is increasing, but it has received less attention compared to older age groups. Moreover, young individuals show a susceptibility to low awareness of cancer screening and prevention[31]. Identifying the landscape of the Chinese HBP cancers burden in this population could improve overall outcomes.

This study aimed to analyze the present prevalence of HBP cancers among young patients in 2019, along with their historical trends over the past three decades, future projections from 2020 to 2035, and the risk factors identified in the GBD study of 2019. We found a markedly elevated number and rates of incidence, mortality, and DALYs among the young male cohort compared to the young female cohort in the case of LC and PC. Meanwhile, the number and rates of GBTC were roughly equal in both sexes of the young population in 2019. The overall trends for LC decreased from 1990 to 2019, while they increased for GBTC and PC during the same period. In the Chinese young population, the ASIR and ASMR are predicted to increase for GBTC and PC in both sexes from 2020 to 2035. Currently, it was anticipated that the ASIR and ASMR would rise in young males for LC, while initially decreasing slightly and then increasing in young females.

Our analysis revealed that young males in China had a higher incidence of HBP cancers compared to females, with this difference being especially significant in LC and PC. Projections showed that the ASR of these cancers is increasing more rapidly among men than women. In contrast, United States data indicates a similar increase in PC among both sexes in Caucasians, but a greater rise among African American females, highlighting racial disparities[32]. Additionally, studies suggest that early-onset HBP cancers differ from late-onset cancers in terms of epidemiology, clinical presentation, and molecular characteristics[33,34]. This finding implies that age should be a key consideration when determining treatment strategies, such as in immunotherapy, where a patient's age can influence clinical response and side effects[35], paving the way for more tailored therapies. Future studies focusing on these differences could deepen our understanding of the prevention, diagnosis, and treatment of early-onset HBP cancers.

Despite a general decline in LC rates, followed by a gradual increase since 2005, the ASR of HBP cancers among young people in China continued to rise, and the underlying reasons warranted further exploration. While improved screening methods have contributed to this rise, they do not fully explain the trend[13]. Younger individuals with HBP cancers are often diagnosed at more advanced stages than older patients, emphasizing the need to explore risk factors specific to early-onset cases[33,34]. Obesity, strongly associated with HBP cancers, is particularly prevalent in China, which has the largest number of obese individuals and the fastest-growing obesity rate[36,37]. Our findings revealed an increasing proportion of deaths and DALYs related to high BMI among young Chinese from 1990 to 2019. While HBV vaccination likely contributes to the pre-2005 decline in LC ASR, the rise of non-alcoholic fatty liver disease (NAFLD) has driven the increase in LC ASR since then, for NAFLD is the only growing aetiology[38]. Obesity also emerged as a significant risk factor for PC among young patients, with studies showing that overweight or obese individuals develop PC 2 to 6 years earlier than those with normal weight[39]. Moreover, smoking and alcohol use were major contributors to early-onset LC and PC, and our analysis revealed a growing prevalence of these risk factors among young Chinese, underscoring the urgent need for targeted youth interventions to help mitigate the risks of LC and PC. Other factors like diet, lifestyle, environmental exposures, and even the microbiome, have also been shown to significantly impact the risk of HBP cancers[40]. Studies also indicate that the carcinogenesis of HBP cancers involves a complex, multi-stage, and multifactorial pathological mechanism. Excessive or premature exposure to risk factors during early life may significantly increase the risk of early-onset HBP cancers[41,42].

To effectively address the rising burden of HBP cancers among young people in China, it is crucial to adopt a comprehensive and multifaceted approach. HBP cancers are often influenced by lifestyle factors established during childhood or adolescence. Therefore, schools and educational institutions should play a pivotal role in promoting healthy diet and lifestyle among youth. This includes providing fresh, nutritious food, encouraging balanced diets, discouraging early exposure to tobacco and alcohol, and promoting regular physical exercise. Moreover, caloric restriction and fasting, which aid in weight loss and diabetes management, can serve as effective preventive measures against HBP cancers in young individuals[36,43-45]. Additionally, government intervention is needed to implement and promote health taxes on tobacco, alcohol, and sugary beverages to reduce their consumption among the youth. Raising awareness about HBP cancers among the younger population, reevaluating current screening guidelines and developing personalized screening methods for early-onset cancers are critical[46]. Molecular and multi-omics analyses of early- and late-onset tumors can shed light on the relationship between specific molecular characteristics and tumor development, as well as how certain exposures may trigger tumors through these molecular pathways[47]. Thus, molecular epidemiological studies on early-onset HBP cancers could provide more sensitive and specific markers for early screening and guide the personalized therapies[47].

We should acknowledge several limitations existing in our study. Firstly, our data were sourced from GBD 2019, which had inherent limitations that might introduce biases and affect the accuracy of the estimates. Secondly, the absence of subtype-specific data for HBP tumors precluded the estimation of the specific impact of tumor subtypes on the incidence of HBP cancers. Lastly, provincial and socio-economic disparities of HBP tumors in China could not be assessed due to the absence of detailed provincial-level data in GBD 2019.

CONCLUSION

In conclusion, this study revealed a heterogeneous burden landscape of HBP cancers among young Chinese adults categorized by gender in 2019. We depicted the changing burden of HBP cancers over the last 30 years, with increasing burdens for GBTC and PC, and a decreasing burden for LC. Furthermore, we predicted an increase in ASIR and ASMR for all HBP cancers in both males and females. However, there is an exemption for LC in females, as it is anticipated to initially decline slightly and then rise. These findings offered updated insights into the burden of HBP cancers among Chinese youth, suggesting strategies and measures for the prevention and management of associated risk factors.

ACKNOWLEDGEMENTS

We are grateful to the numerous individuals who contributed to the Global Burden of Disease Study 2019 in various capacities and to Win Topatana for assisting in revising the manuscript.