Global, regional, and national burden of gastrointestinal cancers in early onset and young women, 1990–2021: analysis of data from the Global Burden of Disease study 2021

Introduction

Gastrointestinal (GI) cancers constitute a substantial percentage of global cancer cases. Stomach, colorectal, pancreatic, esophageal, liver, and gallbladder cancers collectively represent GI cancers, which significantly threaten global public health (1). An analysis of the Global Burden of Disease (GBD) database indicates that in 2021, there were 5.26 million new cases and 3.7 million deaths due to GI cancers (2). The incidence of these tumors varies markedly across various regions. In Asia, the incidence of esophageal, stomach, and liver cancers remains elevated, whereas in Europe and the United States, colorectal and pancreatic cancers exhibit comparatively higher incidence rates (3). GI cancers constitute a substantial percentage of female cancers, as indicated by global cancer statistics for women in 2022. Colorectal cancer (CRC) is the third most common cancer in women, comprising 9.4% of cases, whereas stomach and liver cancers rank fifth and sixth, representing 3.5% and 2.7% of cases, respectively (4).

The prevalence of GI cancers varies markedly across different regions and nations (5). In specific areas, the lack of medical resources and insufficient healthcare services have caused delays in cancer screening and treatment, resulting in increased morbidity and mortality rates from this disease (2,3). An extensive examination of data from 50 national and regional cancer registries indicated that early-onset CRC (diagnosed between the ages of 25 and 49 years) is demonstrating a more significant rise in women than in men in England, Scotland, Turkey, Australia, Norway, and Costa Rica (6). East Asia exhibits the highest prevalence of stomach cancer (SC), whereas African patients are generally younger and have a greater proportion of female cases (7). The areas with the greatest lifetime risk of GI cancers include stomach, esophageal, liver, and gallbladder cancers in East Asia; pancreatic cancer (PC) in Western Europe; and CRC in New Zealand and Australia (8,9). The disparities in the global lifetime risk of GI cancers are ascribed to the inequitable distribution of socio-economic resources, unequal access to healthcare services among nations, and variations in the management of risk factors. Therefore, comprehensive studies and analyses of the burden of GI cancers among early onset and young women in various regions and countries are essential. This is crucial for the formulation of more precise prevention and control strategies.

While gender-specific factors may influence certain cancers, focusing solely on women as a sex is not a critical determinant for GI cancer diagnosis (10). GI cancers affect individuals across all genders, and their diagnosis is more closely linked to factors such as age, lifestyle, and genetic predisposition. Given the limited attention previously afforded to the impact of GI cancers in early onset and young women, our study aims to assess the trends in incidence, prevalence, mortality, and disability-adjusted life years (DALYs) associated with these cancers utilizing data from GBD 2021. The objective is to address the deficiency in global epidemiology, enhance public awareness of women’s health concerns, particularly among those of childbearing age, and establish a scientific foundation for formulating effective strategies to prevent GI cancers in early onset and young women. We present this article in accordance with the STROBE reporting checklist (available at https://jgo.amegroups.com/article/view/10.21037/jgo-2025-229/rc).

Methods

Data source and disease definition

The GBD database, developed by the Institute for Health Metrics and Evaluation (IHME), serves as a crucial resource for assessing contemporary epidemiological data regarding the burden of 371 diseases and injuries (11). Esteemed as one of the most extensive databases for analyzing the GBD, it has been revised to GBD 2021 after multiple enhancements, guaranteeing the availability of timely and dependable data for the formulation of global healthcare policy (12). The pertinent statistical methodologies and principles have been thoroughly delineated in previous studies (13-15), and their data sources have been extensively utilized in the domain of epidemiology. The GBD 2021 dataset is incomplete, with missing data for the 15–19 age group in the esophageal cancer (EC) and gallbladder and biliary tract cancer (GBTC) categories. The data has not been populated to ensure the study’s accuracy. Data on GI cancers were obtained from the International Classification of Diseases 10 (ICD-10) codes: esophageal (C15), stomach (C16), colorectal (C18-21), liver (C22), gallbladder and biliary tract (C23-24), and pancreatic (C25) cancers (16). We focused on early onset and young women aged 15 to 49 years (17). Patients were classified into seven age brackets: 15 to 19, 20 to 24, 25 to 29, 30 to 34, 35 to 39, 40 to 44, and 45 to 49 years. This study obtained and analyzed data regarding the incidence, prevalence, mortality, and DALYs of GI cancers among early onset and young women globally from 1990 to 2021, sourced from the website (http://ghdx.healthdata.org/gbd-results-tool). The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. It involved a secondary evaluation of publicly available data from the GBD study, without any primary data collection. Thus, ethics approval and informed consent were not required.

Age-standardized burden metrics

DALYs are a composite metric that quantifies the total burden of disease and injury on a population. This is accomplished by aggregating years of life lost (YLL) from premature mortality with years lived with disability (YLD) (11). The socio-demographic index (SDI) is a composite metric derived from per capita income, total fertility rate for individuals aged 25 and younger, and average educational attainment, with a scale from 0 to 1 (12,18). The index is classified into five categories: high SDI, high-middle SDI, middle SDI, low-middle SDI, and low SDI. This study calculated the age-standardized rate (ASR) of GI cancers among early onset and young women aged 15 to 49 years, per 100,000 population, utilizing the formula:

ASR=∑i=1NαiWi∑i=1NWi[1]

(α_i: the age-specific rate for the ith age group, w: the number of individuals in the standard population corresponding to the ith age group, and N: the total number of people in the ith age group)

The age-standardized incidence rate (ASIR), age-standardized prevalence rate (ASPR), age-standardized mortality rate (ASMR), and age-standardized DALYs rate (ASDALYR) were employed to characterize the disease burden.

Statistical analysis

The estimated annual percentage change (EAPC) is frequently utilized to monitor variations in variables such as prevalence and incidence over designated time periods (19). The aim of this study was to assess the dynamic trends in incidence, prevalence, mortality, and DALYs of GI cancers among early onset and young women from 1990 to 2021, employing the formula:

y=α+βx+ε[2]

EAPC=100×[exp(β)−1][3]

(x: year, y: the natural logarithm of rates, α: the intercept, β: the slope, ε: the random error)

An EAPC and its 95% confidence interval (CI) exceeding 0 signifies an increasing trend in ASR over time. If the EAPC and its 95% CI are less than 0, this signifies a decreasing trend in ASR. If the 95% confidence interval includes 0, the change in ASR is deemed statistically insignificant. Furthermore, we employed Spearman correlation analyses to evaluate the relationship between ASR and SDI values across 21 regions. All data were analyzed utilizing R software (version 4.4.1).

Results

Global level

Incidence

In 2021, the global incident cases of CRC among early onset and young women were estimated to be 85,224 [95% uncertainty interval (UI): 77,621 to 94,087], EC 9,911 (95% UI: 8,345 to 11,904), GBTC 6,690 (95% UI: 5,153 to 8,133), liver cancer (LC) 15911 (95% UI: 14,055 to 18,086), PC 10,360 (95% UI: 9,456 to 11,303), and 43,336 (95% UI: 38,353 to 49,002) for SC. With regard to ASIR, CRC has the highest incidence rate 4.17 (95% UI: 3.8 to 4.61) per 100,000 in 2021, followed by SC 2.13 (95% UI: 1.89 to 2.41) and LC 0.78 (95% UI: 0.69 to 0.89) per 100,000. The incidence of PC was 0.50 (95% UI: 0.46 to 0.55), EC was 0.48 (95% UI: 0.41 to 0.58), and GBTC were 0.33 (95% UI: 0.25 to 0.40) per 100,000. It is important to note that all six cancers demonstrate a downward trend in ASIR from 1990 to 2021, with the following EAPCs: EAPC of CRC is −0.14 (95% CI: −0.19 to −0.10), EAPC of EC is −2.13 (95% CI: −2.27 to −1.98), EAPC of GBTC is −0.86 (95% CI: −0.92 to −0.80), EAPC of LC −0.95 (95% CI: −1.09 to −0.82), PC −0.45 (95% CI: −0.50 to −0.40), and SC −2.56 (95% CI: −2.60 to −2.52). Among these, SC exhibits the most significant downward trend (Table 1, Figure 1).

Figure 1 The trends in numbers and rates of incidence for gastrointestinal cancers among early onset and young women in global from 1990 to 2021.

Prevalence

In 2021, the global prevalent cases of CRC were 538,787 (95% UI: 490,286 to 595,328), significantly surpassing that of SC, which was 109,786 (95% UI: 96,910 to 125,465), with an ASPR of 26.39 (95% UI: 24.01 to 29.17), compared with 5.41 (95% UI: 4.78 to 6.18) per 100,000 for SC. From 1990 to 2021, there is an increasing trend in the ASPR for CRC with an EAPC of 0.36 (95% CI: 0.32 to 0.39), compared to a decreasing trend for SC, with a EAPC of −2.11 (95% CI: −2.15 to −2.07). In the same year, the prevalence of EC was 28,508 (95% UI: 23,627 to 33,946), compared to LC at 27,907 (95% UI: 24,587 to 31,820) and PC at 14,736 (95% UI: 13,530 to 15,976). And, the ASPR of EC also exceeded that of LC and PC. GBTC had the lowest prevalence and ASPR among these six cancers. From 1990 and 2021, EC, LC, and GBTC ASPR exhibit a declining trend, with their EAPCs recorded at −1.44 (95% CI: −1.62 to −1.27), −0.51 (95% CI: −0.64 to −0.39), and −0.27 (95% CI: −0.33 to −0.22), respectively (Table 1, available online: https://cdn.amegroups.cn/static/public/JGO-2025-229-Supplementary.pdf).

Mortality

In 2021, an estimated 32,145 (95% UI: 29,206 to 35,326) deaths will be attributed to CRC and 29,057 (95% UI: 25,953 to 32,385) to SC. Worldwide, approximately 12,895 (95% UI: 11,430 to 14,607) deaths were ascribed to LC, 8,744 (95% UI: 7,953 to 9,559) to PC, and 7,620 (95% UI: 6,455 to 9,251) to EC. In recent decades, ASMR for CRC has exhibited a declining trend with an EAPC of −1.42 (95% CI: −1.51 to −1.33), in contrast to a more pronounced decrease for EC and SC, with EAPCs of −2.48 (95% CI: −2.64 to −2.33) and −3.02 (95% CI: −3.09 to −2.95), respectively. GBTC and LC experienced a marginal decline, slightly less than CRC, which recorded EAPCs of −1.36 (95% CI: −1.43 to −1.28) and −1.29 (95% CI: −1.45 to −1.14), respectively (Table 1, available online: https://cdn.amegroups.cn/static/public/JGO-2025-229-Supplementary.pdf).

DALYs

Globally, CRC accounted for the highest number of DALYs among GI cancers in 2021 at 1,615,410 (95% UI: 1,465,809 to 1,782,374), followed by SC at 1,447,833 (95% UI: 1,292,637 to 1,611,736), with both cancers accounting for more than 1,000,000. CRC and SC continued to be the top two of the six cancers in terms of ASDALYR, with values of 79.49 (95% UI: 72.1 to 87.75) and 71.45 (95% UI: 63.78 to 79.53) per 100,000, respectively. The ASDALYRs for all six cancers show a decreasing trend from 1990 to 2021, with SC showing the most pronounced EAPC, with a value of −3.00 (95% CI: −3.07 to −2.94) (Table 1, available online: https://cdn.amegroups.cn/static/public/JGO-2025-229-Supplementary.pdf).

SDI regional level

At the SDI regional level, an increasing trend in ASIR for CRC in 2021 was observed, with the largest increase in ASIR and ASPR being seen in the low-middle SDI region, with EAPCs of 0.48 (95% CI: 0.42 to 0.54) and 0.98 (95% CI: 0.93 to 1.03), respectively. Conversely, ASMR and ASDALYR for CRC exhibited predominantly decreasing trends at the SDI level, with the most significant decreases observed at the high-middle SDI region, with EAPCs of −2.02 (95% CI: −2.14 to −1.89) and −1.95 (95% CI: −2.08 to −1.83) for ASDALYR, respectively (Table 2, Figure 2, available online: https://cdn.amegroups.cn/static/public/JGO-2025-229-Supplementary.pdf). In 2021, SC demonstrated a downward trajectory in terms of ASIR, ASPR, ASMR and ASDALYR. SC exhibited the highest ASIR and ASPR in the high-middle SDI region with rates of 2.73 (95% UI: 2.25 to 3.36) and 7.62 (95% UI: 6.19 to 9.50) per 100,000, respectively. Middle SDI region exhibited the largest decline in ASIR with an EAPC of −2.83 (95% CI: −2.90 to −2.75) and high SDI region had the largest decline in ASPR with an EAPC of −2.22 (95% CI: −2.32 to −2.12). Conversely, high-middle SDI ASMR and ASDALYR exhibited the most significant decline, with EAPCs of −3.71 (95% CI: −3.87 to −3.55) and −3.68 (95% CI: −3.84 to −3.53), respectively (Table 2, Figure 2, available online: https://cdn.amegroups.cn/static/public/JGO-2025-229-Supplementary.pdf). The ASIR for EC decreased from 1990 to 2021, with low SDI region exhibiting the highest ASIR at 0.82 (95% UI: 0.57 to 1.07) per 100,000. The ASPR for EC exhibited a downward trend in the majority of the SDI regions, with the exception of high SDI region, which demonstrated an increase, exhibiting an EAPC of 0.65 (95% CI: 0.43 to 0.87). The most pronounced decline was observed in middle SDI region, with an EAPC of −2.50 (95% CI: −2.71 to −2.28). The distribution of the ASMR for EC at the SDI level, was essentially consistent with the distribution trend of ASDALYR, which exhibited a downward trend (Table 2, Figure 2, available online: https://cdn.amegroups.cn/static/public/JGO-2025-229-Supplementary.pdf).

Figure 2 The trends in numbers and rates of incidence for gastrointestinal cancers among early onset and young women by SDI regions from 1990 to 2021. SDI, socio-demographic index.

From 1990 to 2021, LC demonstrated the most substantial decline in ASMR and ASDALYR in the high-middle SDI, exhibiting EAPCs of −2.16 (95% CI: −2.44 to −1.88) and −2.24 (95% CI: −2.52 to −1.96), respectively. Conversely, the middle SDI demonstrated the most substantial decline in ASPR and ASIR, exhibiting EAPCs of −1.24 (95% CI: −1.51 to −0.96) and −1.72 (95% CI: −1.96 to −1.47), respectively. The distribution trends of ASMR and ASDALYR in PC at the SDI level were found to be largely analogous, primarily exhibiting a downward trend in the high-middle SDI, high SDI and middle SDI, while low-middle SDI demonstrated the most significant increase. In both ASMR and ASDALYR, with EAPCs of 1.15 (95% CI: 1.08 to 1.22) and 1.13 (95% CI: 1.07 to 1.20), respectively (Table 2, Figure 2, available online: https://cdn.amegroups.cn/static/public/JGO-2025-229-Supplementary.pdf). Furthermore, it was observed that the increase in ASIR, and the increase in ASPR for PC in the low-middle SDI, with EAPCs of 1.21 (95% CI: 1.14 to 1.28) and 1.34 (95% CI: 1.28 to 1.39), respectively, also ranked first in the SDI regions (Table 2, Figure 2, available online: https://cdn.amegroups.cn/static/public/JGO-2025-229-Supplementary.pdf). For GBTC, the highest ASIR was recorded as 0.37 (95% UI: 0.34 to 0.40) for High SDI and 0.37 (95% UI: 0.27 to 0.50) for Low-middle SDI, with the most significant decline observed in High SDI, exhibiting an EAPC of −1.12 (−1.20 to −1.04). The ASPR of most SDI regions demonstrated a downward trend, with the most significant decrease observed in Low SDI, exhibiting an EAPC of −0.24 (95% CI: −0.32 to −0.16) (Table 2, Figure 2, available online: https://cdn.amegroups.cn/static/public/JGO-2025-229-Supplementary.pdf).

GBD regional level

When analyzed at the level of the 21 GBD regions, it was found that East Asia and South Asia had the highest values of ASIR, ASPR, ASMR, and ASDALYR among the six GI cancers in 2021; specifically, East Asia had the highest incident cases for CRC, SC, LC, and PC, with 23,936 (95% UI: 17,648 to 31,911), 15,137 (95% UI: 11,402 to 20,166), 5,318 (95% UI: 3,935 to 7,050), and 2,576 (95% UI: 1,899 to 3,407), respectively. Conversely, South Asia demonstrated the highest incident cases for EC, and GBTC, in that order: 3,242 (95% UI: 2,623 to 4,554) and 2,212 (95% UI: 1,426 to 2,900). It is also noteworthy that all six GI cancers exhibited the highest prevalent cases in East Asia. The prevalent cases for CRC were 161,428 (95% UI: 119,480 to 214,299), and for SC, it was 42,205 (95% UI: 31,599 to 56,350). In East Asia, CRC, LC, PC and SC exhibited elevated mortality and DALY counts, with SC registering the highest mortality and DALY numbers among these GI cancers, at 8,168 (95% UI: 6,140 to 10,824) and 401,616 (95% UI: 301,450 to 532,420), respectively. Conversely, EC, and GBTC exhibited the highest numbers of mortality and DALY in South Asia, with higher mortality and DALY numbers for EC than for GBTC, with values of mortality 138,777 (95% UI: 111,421 to 196,770) and DALY 2,870 (95% UI: 2,311 to 4,053) (Figures 3,4, available online: https://cdn.amegroups.cn/static/public/JGO-2025-229-Supplementary.pdf).

Figure 3 The numbers of incidence for gastrointestinal cancers among early onset and young women by 21 regions in 1990 and 2021. GBD, Global Burden of Disease.

Figure 4 The rates of incidence for gastrointestinal cancers among early onset and young women by 21 regions in 1990 and 2021. GBD, Global Burden of Disease.

In 2021, the Australasia had the highest ASIR and ASPR for CRC, with an ASIR of 9.37 (95% UI: 7.47 to 11.58) and an ASPR of 68.8 (95% UI: 55.13 to 84.51) per 100,000. The ASMR exhibited a downward trend in the majority of regions, with only a few showing an upward trend. Notably, Tropical Latin America demonstrated the highest ASMR of 2.4 (95% UI: 2.2 to 2.59) per 100,000 and the highest DALY of 119.62 (95% UI: 109.99 to 129.48) per 100,000. For SC, ASIR, ASPR, ASMR and ASDALYR exhibited a downward trend in the majority of regions, with only a few regions demonstrating an upward trend. Among them, ASIR (4.96, 95% UI: 4.2 to 5.88) and ASPR (20.62, 95% UI: 17.39 to 24.44) per 100,000 were highest in High-income Asia Pacific. In 2021, Eastern Sub-Saharan Africa and Southern Sub-Saharan Africa had both the highest ASIR and ASPR for EC. From 1990 to 2021, ASMR and ASDALYR demonstrated a downward trend in most of GBD regions (Figures 3,4, available online: https://cdn.amegroups.cn/static/public/JGO-2025-229-Supplementary.pdf).

In 2021, the highest ASIR and ASDALYR for LC were reported in Southern Sub-Saharan Africa, with an ASIR of 1.92 (95% UI: 1.42 to 2.57) and an ASDALYR of 88.8 (95% UI: 65.41 to 120.32) per 100,000. The ASPR for LC was highest in the High-income Asia Pacific at 2.45 (95% UI: 1.85 to 3.27) per 100,000 and the ASMR was highest in Central Asia at 0.97 (95% UI: 0.80 to 1.17) per 100,000. For PC, ASIR was highest in High-income North America at 0.96 (95% UI: 0.91 to 1.01) per 100,000. In the Western Europe, the ASPR is the highest at 2.07 (95% UI: 1.84 to 2.34) per 100,000, while the ASMR and ASDALYR are both highest in the Eastern Europe at 0.81 (95% UI: 0.71 to 0.95) and 39.03 (95% UI: 33.89 to 45.46) per 100,000, respectively. In 2021, the Andean Latin America has the highest ASIR for GBTC at 0.68 (95% UI: 0.46 to 0.99) per 100,000 and the highest ASDALYR at 25.72 (95% UI: 17.72 to 25.72) per 100,000. The Australasia region had the highest ASPR at 1.87 (95% UI: 1.54 to 2.20) per 100,000 (Figures 3,4, available online: https://cdn.amegroups.cn/static/public/JGO-2025-229-Supplementary.pdf).

In terms of incidence, the burden of GBTC, LC, EC and SC shows a decreasing trend in more than half of the GBD regions over the period 1990–2021, with Southern Latin America showing the most pronounced reduction in the burden of GBTC, with an EAPC of −2.89 (95% CI: −3.08 to −2.69). East Asia shows the greatest decrease in the burden of LC and EC, with EAPCs of −1.98 (95% CI: −2.30 to −1.66) and −4.38 (95% CI: −4.71 to −4.05), respectively, and High-income Asia Pacific had the most significant reduction in SC, with an EAPC of −3.63 (95% CI: −3.75 to −3.51). In contrast, the burden of PC and CRC increased in most regions, with the largest increase in PC in Western Sub-Saharan Africa, with an EAPC of 2.01 (95% CI: 1.93 to 2.10), and CRC in Central Latin America, with an EAPC of 2.21 (95% CI: 2.11 to 2.31) (Figures 3,4, available online: https://cdn.amegroups.cn/static/public/JGO-2025-229-Supplementary.pdf).

National level

In 2021, Monaco has the highest ASIR for CRC, which can reach 11.60 (95% UI: 6.60 to 18.64) per 100,000, while Netherlands has the highest ASPR at 84.46 (95% UI: 66.31 to 104.69) per 100,000. While Afghanistan has the highest ASMR and ASDALYR at 4.38 (95% UI: 1.06 to 8.29) and 218.64 (95% UI: 53.24 to 412.75) per 100,000 respectively. From 1990 to 2021, ASIR, ASPR for CRC showed an increasing trend in most countries and ASMR and ASDALYR showed a decreasing trend in most countries. However, Lesotho had the fastest increase in ASIR, ASPR, ASMR and ASDALYR with EAPCs of 4.71 (95% CI: 3.92 to 5.51), 4.36 (95% CI: 3.72 to 4.99), 4.70 (95% CI: 3.89 to 5.52) and 4.70 (95% CI: 3.89 to 5.51) respectively in the last 32 years. We observed the second fastest growing ASIR in Zimbabwe with an EAPC of 3.4 (95% CI: 2.39 to 4.42) (Figure 5, available online: https://cdn.amegroups.cn/static/public/JGO-2025-229-Supplementary.pdf). Afghanistan had the highest burden of SC with ASIR 14.18 (95% UI: 5.66 to 23.16), ASMR 13.20 (95% UI: 5.34 to 21.65) and ASDALYR 657.94 (95% UI: 266.86 to 1079.97) per 100,000, while Republic of Korea had the highest ASPR of 28.73 (95% UI: 19.68 to 41.16) per 100,000. From 1990 to 2021, ASIR, ASPR, ASMR and ASDALYR of SC showed a decreasing trend in majority of the countries. In addition, Zimbabwe had the fastest growing ASPR with an EAPC of 3.35 (95% CI: 2.24 to 4.48) (Figure 5, available online: https://cdn.amegroups.cn/static/public/JGO-2025-229-Supplementary.pdf). In 2021, Malawi had the highest burden of EC with the highest ASIR, ASPR, ASMR and ASDALYR of 2.93 (95% UI: 1.50 to 5.39), 6.26 (95% UI: 3.36 to 11.61), 2.66 (95% UI: 1.44 to 4.87), and 127.89 (95% UI: 68.78 to 235.53) per 100,000, respectively. ASIR, ASPR, ASMR and ASDALYR for EC showed a decreasing trend in most countries from 1990 to 2021. Zimbabwe had the highest increase in ASIR, ASPR, ASMR and ASDALYR for EC from 1990 to 2021 with EAPCs of 3.65 (95% CI: 2.49 to 4.82), 3.35 (95% CI: 2.24 to 4.48), 3.71 (95% CI: 2.54 to 4.89) and 3.73 (95% CI: 2.56 to 4.91), respectively (Figure 5, available online: https://cdn.amegroups.cn/static/public/JGO-2025-229-Supplementary.pdf).

Figure 5 ASIR for gastrointestinal cancers among early onset and young women across 204 countries and territories in 2021. ASIR, age-standardized incidence rate; CRC, colorectal cancer; GBTC, gallbladder and biliary tract cancer.

The highest ASIR, ASPR, ASDALYR and ASDALYR were reported in LC 2021 in Mongolia with ASIR 8.57 (95% UI: 5.81 to 12.69), ASPR 12.83 (95% UI: 8.65 to 19.12), ASMR 7.95 (95% UI: 5.38 to 11.75) and ASDALYR 400.38 (95% UI: 269.63 to 593.34) per 100,000. From 1990 to 2021, ASIR, ASPR, ASMR and ASDALYR for LC showed a decreasing trend in most countries. However, over the last 32 years, United Kingdom had the fastest growing ASIR and ASPR with EAPCs of 4.52 (95% CI: 4.27 to 4.77) and 5.23 (95% CI: 4.94 to 5.51) respectively (Figure 5, available online: https://cdn.amegroups.cn/static/public/JGO-2025-229-Supplementary.pdf). Statistically, for PC, Palau is estimated to have the highest ASIR 2.06 (95% UI: 1.29 to 3.22) and ASDALYR 90.39 (95% UI: 55.98 to 143.28) per 100,000, while Germany has the highest ASPR 3.73 (95% UI: 2.78 to 4.86) and ASMR 1.82 (95% UI: 1.13 to 2.86) per 100,000. From 1990 to 2021, ASIR, ASPR, ASMR and ASDALYR of PC showed an increasing trend in most of the countries. The greatest increase in ASIR, ASPR, ASMR and ASDALYR of PC was observed in Mongolia with EAPCs of 7.01 (95% CI: 6.07 to 7.95), 7.41 (95% CI: 6.43 to 8.40), 6.96 (95% CI: 6.03 to 7.90) and 7.08 (95% CI: 6.13 to 8.04) in the last 32 years (Figure 5, available online: https://cdn.amegroups.cn/static/public/JGO-2025-229-Supplementary.pdf). In contrast, Chile had the highest burden of GBTC, with an ASIR of 1.61 (95% UI: 1.26 to 2.02) per 100,000, an ASPR of 3.00 (95% UI: 2.30 to 3.83) per 100,000. From 1990 to 2021, ASIR, ASPR, ASMR and ASDALYR for GBTC have shown a decreasing trend in most countries (Figure 5, available online: https://cdn.amegroups.cn/static/public/JGO-2025-229-Supplementary.pdf).

Age patterns

In 2021, the age distribution of GI cancers in early onset and young women is generally consistent in terms of incidence, prevalence, mortality and DALYs. Specifically, the incidence, prevalence, mortality, and DALYs of these six GI cancers increase with age, and, all peak in the 45–49 years age group. Moreover, when we analyzed in depth the age group 45–49 years, the number of incidence and cases of CRC was the highest with 36,038 (95% UI: 32,974 to 39,651) new cases in the year 2021 only, with an incidence rate of 15.29 (95% UI: 13.99 to 16.83) per 100,000. SC had incident numbers of 15,487 (95% UI: 13,721 to 17,590), with an incidence of 6.57 (95% UI: 5.82 to 7.46) per 100,000. CRC among 45–49 years age group tops the list for prevalence. The prevalent number of CRC among WBCA in this age group in 2021 is 224,724 (95% UI: 205,820 to 247,665), with a prevalence of 95.37 (95% UI: 87.34 to 105.10) per 100,000, whereas the number of SC patients in the second place is 35,732 (95% UI: 31,669 to 41,031), which is only 16 per cent of the CRC population. The prevalence of SC was 15.16 (95% UI: 13.44 to 17.41) per 100,000. In terms of mortality, the top two WBCA GI cancers in terms of number and rates of deaths for 45–49 years age group were CRC and SC, with the number of deaths for both cancers exceeding 10,000. These patterns suggest that GI cancers burdens, especially CRC and SC are increasingly affecting WBCA, especially in the 45–49 years age group WBCA (available online: https://cdn.amegroups.cn/static/public/JGO-2025-229-Supplementary.pdf).

The association between GI cancers and SDI

During 1990–2021, GI cancers among WBCA showed different trends in the 21 GBD regions ASIR. Among them, EC and LC mainly showed decreasing trends. For EC, its ASIR shows an upward trend when the SDI is around 0.45, and then starts to decline when the SDI grows close to 0.6. For LC, the ASIR appears to rise when the SDI is around 0.5 and 0.75. CRC overall rose as the SDI increased. When the SDI increased, the total ASIR for CRC, SC, and PC declined and then increased, and it is noteworthy that PC rose more rapidly than the other two cancers. GBTC also trend upward overall, but show a small decline at SDIs of about 0.5 and 0.7. And, we found that the ASPRs for these six GI cancers in 2021 in 21 GBD Regions broadly show similar trends as described above. In addition, the same similar association between ASMR and ASDALYR was observed in the relationship between GI cancers and SDI in WBCA. Specifically, overall ASMR and ASDALYR showed negative trends with SDI for LC and EC cancers. EC, however, showed a positive increase as the SDI approached 0.5. LC, on the other hand, showed two increases, at SDI close to 0.6 and 0.75, respectively. The ASMR and ASDALYR of PC were both decreasing and then rapidly increasing (Figure 6, available online: https://cdn.amegroups.cn/static/public/JGO-2025-229-Supplementary.pdf).

Figure 6 The associations between the SDI and ASIR (A), ASPR (B), ASDALYR (C), and ASMR (D) of colorectal cancer among early onset and young women across 21 regions. ASDALYR, age-standardized disability-adjusted life years rate; ASIR, age-standardized incidence rate; ASMR, age-standardized mortality rate; ASPR, age-standardized prevalence rate; SDI, socio-demographic index.

Discussion

GI cancers have attracted considerable attention globally due to the enormous burden they impose on humans (20). GBD 2021 is a new version of the 2019 version with newly added disease data profile for 2019–2021 (21). In this study, we accessed the GBD 2021 database to collect data on GI cancers in early onset and young women from 1990–2021, and analyzed their incidence, prevalence, mortality and DALY data by collating and analyzing them into global, regional and national levels to provide a comprehensive assessment of the burden of GI cancers in women aged 15–49 years. The main findings are as follows: first, from 1990 to 2021, the ASIR, ASMR and ASDALYR of six cancers among WBCA are showing a decreasing trend, and it is noteworthy that ASIR, ASMR and ASDALYR of SC have the largest decrease. Second, among GI cancers diseases in the global WBCA in 2021, CRC demonstrated the highest ASIR, ASPR, ASMR and ASDALYR, and only CRC and PC showed an increasing trend in prevalence. Third, among GI cancers, basically High SDI ASIR and ASPR were higher, whereas ASDALYR and ASMR was mainly concentrated in Low SDI and Low-middle SDI. Fourth, among the 21 GBD regions in 2021, East Asia and South Asia had the highest incidence, prevalence, mortality and DALY numbers among the six GI cancers. Fifth, at the national level, there was significant variability in the burden of six GI cancers among WBCA. Sixth, the 45–49 years age group had the highest burden, especially for CRC.

In 2021, in 21 GBD regions, the ASIR of CRC demonstrated a consistent upward trajectory alongside increased SDI, corroborating prior findings that elevated CRC incidence and prevalence are concentrated in high SDI regions and nations (22). CRC is primarily linked to various behavioral factors, including elevated body mass index (BMI), hyperinsulinemia diets, sedentary lifestyles, and reduced physical activity levels (23,24). A substantial cohort study has demonstrated that BMI correlates with CRC more significantly in premenopausal women than in postmenopausal women (25). The ASMR and ASDALYR for CRC exhibited a nonlinear correlation with SDI, indicating that the burden of CRC does not necessarily diminish in nations with elevated economic status. Alongside common factors, the advancement and proliferation of medical technology, including the extensive implementation of colonoscopies and the development of cancer registries, may also contribute to the consistently elevated prevalence of CRC (26). In contrast, populations in nations with elevated economic status priorities their health and exhibit a readiness to participate in preventive health measures, such as medical examinations, leading to a steady influx of CRC patients undergoing screening. As research advances, targeted and immunotherapy methods (27,28) for CRC have evolved, leading to a notable enhancement in patient survival rates. This is evident in the significant reduction in ASMR and ASDALYR noted after SDI surpasses 0.75. Nonetheless, some SDI correlation analyses suggest that the management of CRC should remain uncompromised, even in affluent regions. Between 1990 and 2010, there was a significant rise in the consumption of unhealthy foods, outpacing the growth of healthy foods. This trend suggests that younger women may encounter significant difficulties in achieving optimal dietary quality relative to older age cohorts (29). An analysis of epidemiological data reveals that 32% of CRC-related deaths and 34% of DALYs for CRC are linked to dietary risk factors (30). These figures have exceeded the burden of CRC attributable to smoking and alcohol consumption. Embracing a healthy lifestyle, including dietary changes, is a crucial approach to preventing the onset of CRC in early onset and young women. This strategy is crucial for alleviating the global burden of CRC.

Over the past 32 years, the WBCA has exhibited a decreasing trend in the burden of SC, as indicated by ASIR, ASMR, and ASDALYR, with the most pronounced reduction noted among all cancers. Zhang et al. employed the GBD data resource to examine the incidence and mortality of SC by gender, revealing a decline in the 15–49 age group, which aligns with our study’s findings (31). The significant reduction in the burden of SC over the last 32 years is promising. Numerous studies (32,33) indicate that temporal trends and geographic disparities in the incidence of SC are primarily due to alterations in behavioral and environmental risk factors, such as dietary changes (e.g., increased consumption of fruits and vegetables, reduced salt intake), upper GI endoscopic screening, and enhanced hygiene practices. The successful treatment and prevention of Helicobacter pylori (HP) infection has decreased mortality from SC (34,35). GLOBOCAN 2022 (https://www.wcrf.org/) reports that the ASIR for SC in Korean women was 16.9 per 100,000, ranking as the second highest globally and aligning with our findings (4). The traditional Korean diet is marked by a significant intake of salt-rich foods, pickles, and fermented items. Prior research has demonstrated a notable correlation between the consumption of these foods and an increased risk of SC in early onset and young women (36). Existing research has established that nitrite and elevated salt levels in these foods can lead to gastric mucosal injury, which may elucidate the associated carcinogenic risk (37).

This study’s findings indicate a reduction in the overall ASIR and ASPR of EC as SDI increases, thereby supporting the widespread belief that EC primarily affects economically disadvantaged areas. In addition to dietary habits (38), EC is linked to poor environmental exposures, genetic predispositions, and insufficient hygiene practices (39,40). The restricted access to fundamental medical facilities and the exodus of proficient medical personnel from underdeveloped areas are recognized as obstacles to prompt intervention for EC. The noted reduction in ASMR and ASDALYR with rising SDI highlights the effectiveness of socio-economic advancement in alleviating EC mortality and DALY. In East Asia, the incidence of EC is notably high in absolute terms and is closely linked to traditional dietary patterns. The intake of foods and beverages cooked at elevated temperatures, along with salted or cured meats, has been shown to elevate the risk of EC, partly due to these dietary habits resulting in human exposure to nitrosamines and other chemical carcinogens (41). In sub-Saharan Africa, tobacco and alcohol exposure constitutes a significant risk factor alongside dietary influence (42). The region encounters obstacles including inadequate medical facilities and socioeconomic impediments that obstruct early detection and intervention (43). Resolving these issues requires the execution of specific public health strategies, global collaboration to diminish exposure, and the commencement of early screening to alleviate disease risk in early onset and young women.

LC is regarded as one of the most aggressive tumors that warrants immediate attention. Chronic hepatitis B virus (HBV) infection continues to be a significant risk factor for hepatocellular carcinoma (HCC) in Africa, especially in the sub-Saharan area (44). The extensive prevalence of HBV has resulted in a notable rise in the incidence of LC among early onset and young women. The absence of systematic cancer screening and surveillance systems has led to a scarcity of early diagnoses, with most cases advancing to later stages by the time of diagnosis (45). Economic limitations and cultural perceptions further obstruct treatment accessibility, intensifying the elevated morbidity and mortality rates of LC (46,47). Although public health initiatives, such as hepatitis B vaccination, have resulted in a global decrease in new infections, chronic infection continues to pose a significant health challenge (48). Vaccination has effectively mitigated mother-to-child transmission pathways, while rigorous screening protocols for blood and organ donors have substantially diminished the risk of transfusion-related hepatitis (49). The UK exhibits the most significant rise in ASIR, potentially linked to the epidemics of alcohol consumption and obesity. Hospitalization rates for alcoholic liver disease in the UK increased by 43% from 2002 to 2019, while social isolation and psychological stress during the COVID-19 pandemic have exacerbated alcohol consumption in numerous European countries and the United States, potentially elevating the risk of developing alcoholic liver disease (50). The UK Biobank (UKB) cohort study established that genetic liver fat deposition and visceral fat accumulation are positively correlated with the risk of LC (51). It is imperative to create a risk-stratified screening system, execute extensive lifestyle interventions, and concurrently advance the research and development of novel therapies while addressing social determinants of health to effectively alleviate the burden of LC among early onset and young women.

The notable rise in ASIR for PC in low-middle SDI regions is chiefly due to improved diagnosis, lifestyle changes, and the ageing population (52,53). High-income North America persist in demonstrating the highest incidence rates, potentially linked to more efficient case reporting systems and the extensive adoption of screening protocols (54). Research has identified smoking, elevated BMI, and increased fasting glucose as critical risk factors for PC (9). Carcinogens, including nitrosamines found in tobacco smoke, facilitate carcinogenesis by inducing oxidative stress and cellular damage (55,56), resulting in a 75% heightened risk of disease development in smokers compared to non-smokers (57). Insulin resistance caused by excessive body fat and elevated fasting plasma glucose levels increases insulin and insulin-like growth factor concentrations, which suppress apoptosis and fosters tumor proliferation (58,59). The advancement of improved screening and prevention strategies targeting the aforementioned interventional risk factors will substantially reduce the burden of PC in early onset and young women (60).

Geographic disparities in the epidemiological burden of GBTC have been recognized, with the most pronounced reductions in ASMR and ASDALYR occurring in high-income-declaration regions (61,62). These findings may be due to increased awareness of health management practices and improved access to healthcare services among the populations in these developed regions. Surgical interventions like cholecystectomy and choledochectomy, commonly performed in middle- and high-income nations, have demonstrated efficacy in reducing the risk of GBTC in patients with gallstones (63). The prevalence of gallstones during reproductive years is twice as high in women compared to men, which, along with the markedly elevated risk of gallbladder cancer in older women, highlights the gender-specific risk profile (64,65). Populations in developed regions are more prone to obesity due to high-calorie diets, sedentary lifestyles, and metabolic stress. Moreover, obesity rates in women typically exceed those in men, attributable to hormonal levels, gut microbiota, and genetic predisposition, which constitute a metabolic anomaly that intensifies the risk of GBTC (66-68). Consequently, the formulation of targeted preventive intervention strategies for early onset and young women is of substantial public health importance to mitigate the burden of GBTC.

The diagnosis of cancer constitutes a significant health crisis for early onset and young women, who confront not only the immediate peril of GI cancers but also possible reproductive health hazards. This study identified distinct epidemiological characteristics of GI cancers in early onset and young women, establishing a scientific foundation for the formulation of targeted preventive strategies, including health education, lifestyle modification, and vaccination. The examination of the biological traits and pathogenesis of tumors in this cohort will enhance the refinement of screening and testing protocols, thereby elevating the early diagnosis rate and augmenting clinical prognosis. The government should implement a specialized health protection system to alleviate social and economic burdens by enhancing the three-tier disease prevention network. The health status of early onset and young women is directly linked to the safety of mothers and infants; thus, conducting epidemiological studies on GI cancers holds significant public health importance for enhancing maternal and child health.

This study has the following limitations. The analytical results are significantly contingent upon the precision of the GBD database, whose quality is constrained by the availability of registry data and the prevalence of undiagnosed GI cancer cases in each nation. Secondly, data regarding EC and GBTC for the 15–19 years age group were absent in the GBD 2021 dataset, potentially compromising the study’s completeness. Thirdly, data deficiencies in certain areas, especially in less developed nations, may result in an underappraisal of the actual disease burden of GI cancers in these locales. Ultimately, variations in data collection methodologies from diverse sources and the absence of comprehensive histological stratification details in certain datasets may affect the cross-sectional comparability of the study findings.

Conclusions

The prevalence of GI cancers in early onset and young women exhibits significant geographic variation, closely associated with SDI levels and tumor types. From 1990 to 2021, ASIR, ASMR, and ASDALYR of GI cancers among early onset and young women demonstrated a decreasing trend with the most notable reduction in SC. However, the rising incidence of CRC highlights its growing public health challenge. Clinically, our results emphasize the importance of early screening and personalized treatment plans for GI cancers in young women. Healthcare providers should be vigilant about CRC risk factors, such as lifestyle and dietary habits, and consider early intervention strategies. Additionally, improving public awareness of GI cancer symptoms and risk factors can facilitate earlier diagnosis and better patient outcomes.

Acknowledgments

We extend our appreciation to the Institute for Health Metrics and Evaluation for granting access to the essential GBD (the Global Burden of Disease) data.

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://jgo.amegroups.com/article/view/10.21037/jgo-2025-229/rc

Peer Review File: Available at https://jgo.amegroups.com/article/view/10.21037/jgo-2025-229/prf

Funding: This work was supported by the National Natural Science Foundation of China (Nos. 82374539, 81973523), Key Project of Jiangsu Traditional Chinese Medicine Science and Technology Development Plan (No. ZD202214), Jiangsu Traditional Chinese Medicine Leading Talents Training Object Project (No. SLJ0327), Nanjing University of Traditional Chinese Medicine Gastric Cancer Clinical Specialized Research Institute Project (No. LCZBYJYZZ2024-001).

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jgo.amegroups.com/article/view/10.21037/jgo-2025-229/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. It involved a secondary evaluation of the publicly available data from the Global Burden of Disease (GBD) Study, without any primary data collection. Thus, ethics approval and informed consent were not required.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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