Global burden landscape (1990–2021) of gallbladder and biliary tract cancer attributable to high body mass index in older adults and a projection to 2050
Original Article

Global burden landscape (1990–2021) of gallbladder and biliary tract cancer attributable to high body mass index in older adults and a projection to 2050

Pingping Chen1,2#, Wenhao Qin1#, Bing Hu1

1Department of Gastroenterology, Eastern Hepatobiliary Surgery Hospital, Naval Medical University, Shanghai, China; 2Changzheng Hospital, Naval Medical University, Shanghai, China

Contributions: (I) Conception and design: All authors; (II) Administrative support: All authors; (III) Provision of study materials or patients: P Chen, W Qin; (IV) Collection and assembly of data: W Qin; (V) Data analysis and interpretation: P Chen; (VI) Manuscript writing: All authors; (VII) Final approval of manuscript: All authors.

#These authors contributed equally to this work as co-first authors.

Correspondence to: Pingping Chen, MD; Bing Hu, MD. Department of Gastroenterology, Eastern Hepatobiliary Surgery Hospital, Naval Medical University, No. 225 Changhai Road, Shanghai 200438, China; Changzheng Hospital, Naval Medical University, Shanghai, China. Email: chenpingping1124@outlook.com; drhubing@aliyun.com.

Background: Obesity and population aging significantly influence the disease burden of gallbladder and biliary tract cancers (GBTCs). The burden of GBTC attributable to a high body mass index (BMI) among older adults was determined using data from the Global Burden of Disease (GBD) Study 2021.

Methods: GBTC trends in deaths, disability-adjusted life years (DALYs), and age-standardized ratios (ASRs) were examined for different populations, geographic regions, and socio-demographic index (SDI) levels. Stratified clustering by estimated annual percentage change (EAPC) was used to assess patterns of change in the burden of disease in different geographic regions. Predictive modeling was performed using autoregressive integrated moving average modelling to estimate future disease burden.

Results: A total of 360,029 DALYs and 17,976 deaths were attributed to high BMI-related GBTC among older adults globally in 2021. Sex analysis showed that older women had a higher burden of disease, whereas the burden of disease had increased among older men over the last three decades. Moreover, the burden of disease had been heaviest in areas with high SDI, while it had increased significantly in countries with low and medium SDI. Regional analyses of GBD data showed that Asia had the highest burden of disease.

Conclusions: The global burden of GBTC due to high BMI in older adults over the past three decades was comprehensively analyzed. Targeted public health strategies should be implemented to reduce this burden.

Keywords: Gallbladder and biliary tract cancer (GBTC); high body mass index (high BMI); elderly population; projection; socio-demographic index (SDI)

Submitted Nov 06, 2025. Accepted for publication Mar 16, 2026. Published online Apr 26, 2026.

doi: 10.21037/jgo-2025-aw-915

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Key findings

• Gender analysis showed that older women have a higher burden of high body mass index (BMI)-related gallbladder and biliary tract cancers (GBTC) than men. The burden of high BMI-related GBTC has increased among older men during the last three decades, especially in high socio-demographic index (SDI) areas, and in countries with a low and medium SDI.

What is known and what is new?

• Obesity and population aging significantly influence the disease burden of gallbladder and bile duct cancers (GBTC).

• The GBTC burden due to elevated BMI had drastically increased globally among older people. This disease burden remained particularly high among women and in regions with a high SDI. However, the increasing burden trend was more pronounced and unfavorable among men and in regions with low-to-moderate SDI

What is the implication, and what should change now?

• In older age groups, elevated BMI is often closely associated with coexisting conditions such as diabetes and fatty liver disease, which can be potential risk factors for the burden of GBTC.

• It is important to monitor increasing burden trend in different areas during the ongoing growth of global obesity rates and aging populations. Corresponding strategies to various areas or countries should be implemented according to their actual situation.

Introduction

Gallbladder and biliary tract cancers (GBTC) are a category of malignant gastrointestinal tumors, including extrahepatic cholangiocarcinoma, intrahepatic cholangiocarcinoma, and gallbladder cancer, with a high mortality rate (1,2). Epidemiological trends with respect to GBTC indicate significant variations in population, incidence, and mortality rates in different geographic regions (3).

The global incidence of GBTC has been reported to increase with age, especially in high-income countries, suggesting a substantial increase in the cancer burden in these regions (3). Studies have shown that individuals >65 years of age are at greater risk of developing GBTC with a median age at diagnosis usually between 70 and 75 years (4-6). This finding reflects the cumulative effects of age-related changes in the biliary system, including gallstones, inflammation, and other factors that may contribute to cancer development. Older adults frequently have comorbidities, such as diabetes, obesity, or cirrhosis, which can exacerbate the risk of biliary tract and gallbladder cancer (5,6). These pre-existing conditions may interact in complex ways with cancer risk, leading to earlier or more severe disease progression (4-6).

In recent years, the global incidence of obesity has risen in the elderly population, primarily driven by economic growth, urbanization, changing dietary habits, and decreased physical activity, becoming a major cause of the rising incidence of GBTC (7). A largescale analysis of 21 cohort studies in populations from Asia found that an elevated body mass index (BMI) significantly increases GBTC-related deaths, particularly among women, and is associated with increased mortality even in the absence of gallstones (8). GBTC attributable to an elevated BMI in China has greatly increased over the last 30 years along with the accelerated population growth, intensified aging, and epidemiologic shifts (9).

Therefore, it is crucial to better understand GBTC burden associated with elevated BMI in older adults. In the current study, the GBTC burden due to elevated BMI among the elderly population was assessed and stratified by sex, age, socio-demographic index (SDI), and geographic region. Global spatial and temporal patterns were examined from 1990 to 2021, and projections of the disease burden were made for the period of 2022–2050. The findings of this study provide critical insights for health professionals and policymakers in developing targeted public health strategies to reduce this significant and growing disease burden.

Methods

Overview

Data were acquired from the Global Burden of Disease (GBD) 2021 study database, which includes the annual number of GBTC cases and corresponding age-standardized ratios (ASRs) associated with an elevated BMI. The database provides comprehensive epidemiological estimates of the burden of 371 injuries and diseases in 21 GBD regions and 204 countries and territories from 1990 to 2021. All data are freely accessed through the Global Health Data Exchange (https://ghdx.healthdata.org/gbd-2021/sources) (10). The GBD database has obtained the patients’ consents to keep their data. This study was waived by the ethical committee of our institutional review board because of the use of data from a publicly available database. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments.

Definitions

The age group ≥55 years of age is frequently used as a critical reference point for evaluating health characterization patterns among older adults (11), because 55 years of age is widely recognized as the onset of aging due to a strong association with an increasing disease risk and the progressive decline in physiologic functions (12). An elevated BMI is age-dependent according to the GBD definition for adults ≥20 years of age, in which a healthy BMI is between 25 and 30 kg/m2 (13). The SDI is used to assess the burden of diseases related to societal development (14). The SDI is a composite indicator that was launched in 2015 by the Institute for Health Metrics and Evaluation (IHME). The SDI reflects a region’s level of development by looking at the relationship between social progress and health outcomes (15). The SDI is obtained by calculating the geometric mean of three indices: the total fertility rate of the population <25 years of age; the mean level of education attained by the population ≥15 years of age; and the per capita income of the lagged distribution (15). The SDI values ranged from 0 to 100, in the 2021 GBD data, where a small number represents low income, level of education, and high fertility, and a large number represents high income, level of education, and low fertility (16,17). All 204 countries and regions in the GBD database were classified as follows based on the SDI values: low, medium, and high.

Statistical analysis

First, the 2021 GBD dataset provides information on the number of deaths and disability-adjusted life years (DALYs) associated with GBTC attributable to elevated BMI and the corresponding ASRs categorized by age, sex, SDI, region, and country. Second, temporal trends in disease burden were analyzed globally and by subtype from 1990–2021 using the estimated annual percentage change (EAPC) values derived from linear regression models (18). Hierarchical clustering based on EAPC values was then applied to assess patterns of change in disease burden across GBD regions, grouping the EAPC values into four categories: significant increase; slight increase; stability or slight decrease; and significant decrease (19).

Autoregressive integrated moving average modelling (ARIMA), a data-driven approach to predicting future trends based on current patterns, can be used to project the global burden of GBTC due to an elevated BMI from 2022–2050 (20). The ARIMA model is characterized by three parameters (p, d, and q), where p represents the autoregressive term, d denotes the differencing order to stabilize the time series, and q indicates the order of the moving average (21).

Results

Global burden of GBTC attributable to an elevated BMI in older adults

The worldwide distributions of GBTC deaths and DALYs due to an elevated BMI, along with the age-standardized death rate (ASDR) and age-standardized disability-adjusted life years (ASDALY), are summarized by the SDI level for older groups in Tables 1,2.

Table 1

Number of death cases and age-standardized death rate attributable to an elevated body mass index among older adults in 1990 and 2021 with trends observed globally from 1990–2021

Items 1990 2021 1990–2021
Number of death cases [95% UI] Age-standardized death rate/100,000 [95% UI] Number of death cases [95% UI] Age-standardized death rate/100,000 [95% UI] EAPC (95% CI)
Global 8,549 [5,871–11,747] 1.27 [0.87–1.75] 17,976 [12,197–24,938] 1.21 [0.82–1.68] −0.31 (−0.38, 0.24)
Gender
   Female 5,938 [4,042–8,162] 1.65 [1.12–2.27] 10,934 [7,382–15,355] 1.39 [0.94–1.95] −0.74 (−0.82, 0.66)
   Male 2,611 [1,821–3,585] 0.84 [0.58-1.15] 7,042 [4,674–10,019] 1.01 [0.67–1.43] 0.52 (0.48, 0.57)
Age, years
   55–59 868 [601–1,177] 0.47 [0.32–0.64] 1,699 [1,149–2,331] 0.43 [0.29–0.59] −0.38 (−0.47, 0.28)
   60–64 1,264 [867–1,723] 0.79 [0.54–1.07] 2,274 [1,561–3,162] 0.71 [0.49–0.99] −0.43 (−0.54, 0.32)
   65–69 1,494 [1,029–2,030] 1.21 [0.83–1.64] 2,869 [1,943–3,977] 1.04 [0.7–1.44] −0.65 (−0.76, 0.55)
   70–74 1,407 [964–1,900] 1.66 [1.14–2.24] 3,105 [2,107–4,315] 1.51 [1.02–2.1] −0.63 (−0.72, 0.54)
   75–79 1,565 [1,077–2,137] 2.54 [1.75–3.47] 2,748 [1,887–3,795] 2.08 [1.43–2.88] −0.63 (−0.72, 0.54)
   80–84 1,091 [741–1497] 3.09 [2.1–4.23] 2,273 [1,531–3,229] 2.6 [1.75–3.69] −0.64 (−0.74, 0.54)
   85–89 604 [399–848] 3.99 [2.64–5.61] 1,742 [1,119–2,490] 3.81 [2.45–5.45] −0.25 (−0.34, 0.16)
   90–94 208 [134–295] 4.87 [3.13–6.88] 924 [568–1,342] 5.17 [3.18–7.5] 0.11 (0.03, 0.19)
   95+ 47 [29–68] 4.66 [2.89–6.68] 341 [193–497] 6.26 [3.55–9.12] 0.94 (0.86, 1.03)
SDI region
   High-middle SDI 2,692 [1,839–3,712] 1.56 [1.07–2.15] 5,078 [3,378–7,177] 1.46 [0.97–2.07] −0.42 (−0.53, 0.31)
   High SDI 3,986 [2,731–5,516] 2.14 [1.46–2.96] 5,991 [3,899–8,480] 1.74 [1.13–2.46] −0.86 (−0.98, 0.75)
   Low-middle SDI 463 [318–674] 0.46 [0.32–0.67] 1,967 [1,304–2,695] 0.82 [0.54–1.12] 2.02 (1.96, 2.07)
   Low SDI 83 [53–126] 0.22 [0.14–0.34] 307 [186–432] 0.37 [0.23–0.53] 1.83 (1.78, 1.88)
   Middle SDI 1,306 [895–1,817] 0.75 [0.52–1.05] 4,612 [3,114–6,377] 0.98 [0.66–1.36] 0.73 (0.67, 0.8)

CI, confidence interval; EAPC, estimated annual percentage change; SDI, socio-demographic index; UI, uncertainty interval.

Table 2

Number of DALYs cases and the age-standardized DALYs rate attributable to an elevated body mass index among older adults in 1990 and 2021 with trends observed globally from 1990–2021

Items 1990 2021 1990–2021
Number of DALYs cases [95% UI] Age-standardized DALYs rate/100,000 [95% UI] Number of DALYs cases [95% UI] Age-standardized DALYs rate/100,000 [95% UI] EAPC (95% CI)
Global 178,831 [122,678–244,462] 26.63 [18.27–36.41] 360,029 [247,067–498,369] 24.23 [16.63–33.54] −0.46 (−0.54, 0.38)
Gender
   Female 121,843 [82,715–166,637] 33.85 [22.98–46.3] 216,446 [146,540–304,104] 27.52 [18.63–38.67] −0.87 (−0.97, 0.77)
   Male 56,988 [39,711–78,111] 18.3 [12.75–25.08] 143,583 [94,194–204,527] 20.53 [13.47–29.24] 0.29 (0.24, 0.33)
Age, years
   55–59 29,302 [20,293–39,717] 15.82 [10.96–21.45] 57,570 [39,023–78,963] 14.55 [9.86–19.95] −0.37 (−0.46, 0.27)
   60–64 36,814 [25,246–50,279] 22.92 [15.72–31.3] 66,444 [45,709–92,299] 20.76 [14.28–28.84] −0.42 (−0.53, 0.31)
   65–69 36,727 [25,284–49,933] 29.71 [20.45–40.4] 70,734 [47,936–98,086] 25.64 [17.38–35.56] −0.64 (−0.75, 0.53)
   70–74 28,488 [19,530–38,435] 33.65 [23.07–45.4] 63,059 [42,882–87,625] 30.64 [20.83–42.57] −0.62 (−0.71, 0.53)
   75–79 25,282 [17,382–34,496] 41.07 [28.24–56.04] 44,628 [30,708–61,464] 33.84 [23.28–46.6] −0.62 (−0.7, 0.53)
   80–84 13,880 [9,437–19,024] 39.24 [26.67–53.78] 28,979 [19,517–41,114] 33.09 [22.28–46.94] −0.63 (−0.73, 0.54)
   85–89 6,108 [4,045–8,579] 40.42 [26.77–56.78] 17,654 [11,356–25,287] 38.61 [24.84–55.31] −0.25 (−0.33, 0.16)
   90–94 1,836 [1,178–2,595] 42.85 [27.5–60.57] 8,179 [5,030–11,953] 45.72 [28.12–66.82] 0.13 (0.05, 0.21)
   95+ 393 [243–563] 38.59 [23.82–55.3] 2,781 [1,580–4,055] 51.03 [28.99–74.39] 0.88 (0.79, 0.98)
SDI region
   High-middle SDI 57,736 [39,349–79,377] 33.47 [22.81–46.01] 102,337 [68,090–143,609] 29.52 [19.64–41.42] −0.65 (−0.75, 0.55)
   High SDI 77,844 [53,138–106,773] 41.75 [28.5–57.26] 104,300 [68,697–146,351] 30.23 [19.91–42.42] −1.24 (−1.35, 1.12)
   Middle SDI 29,998 [20,492–41,903] 17.28 [11.81–24.14] 100,703 [68,106–139,050] 21.43 [14.49–29.59] 0.56 (0.48, 0.64)
   Low-middle SDI 10,813 [7,380–15,707] 10.73 [7.32–15.58] 45,045 [29,313–61,791] 18.68 [12.16–25.63] 1.95 (1.9, 2)
   Low SDI 2,043 [1,302–3,075] 5.48 [3.49–8.24] 7,223 [4,356–10,094] 8.8 [5.31–12.3] 1.64 (1.6, 1.68)

CI, confidence interval; DALYs, disability-adjusted life-years; EAPC, estimated annual percentage change; SDI, socio-demographic index; UI, uncertainty interval.

In 2021, an estimated 360,029 DALYs [95% uncertainty interval (UI): 5,871–11,747 deaths] and 17,976 deaths (95% UI: 122,678–244,462 DALYs) among older people worldwide were associated with GBTC due to an elevated BMI. The ASDR for an elevated BMI-related GBTC in this demographic was estimated at 1.21 per 100,000 (95% UI: 0.87–1.75) and the ASDALY was estimated at 24.23 per 100,000 (95% UI: 18.27–36.41).

Global deaths due to GBTC associated with an elevated BMI in older adults increased by 110.3%, rising from 8,549 cases in 1990 to 17,976 cases in 2021. Over the same period, the ASDR decreased slightly from 1.27 to 1.21 per 100,000 with a global EAPC of −0.31 [95% confidence interval (CI): −0.38 to −0.24]. The DALY estimates followed a similar trend, with a 101.3% increase in cases and a decline in age-standardized DALYs from 26.63 to 24.23 per 100,000, corresponding to a global EAPC of −0.46 (95% CI: −0.54 to −0.38; Tables 1,2).

Global burden of GBTC attributable to an elevated BMI in older adults: a sex-stratified analysis

In 2021, the global GBTC deaths due to an elevated BMI among older females totaled 10,934 (95% UI: 7,382–15,355), with associated DALYs reaching 216,446 (95% UI: 146,540–304,104). Among older males, there were 7,042 deaths (95% UI: 4,674–10,019; Table 1) and 143,583 DALYs (95% UI: 94,194–204,527; Table 2). The deaths and DALYs for females were 1.55 and 1.51 times higher than for males, respectively, with corresponding ASRs of 1.38 and 1.34 times higher than for males, respectively (Figure 1A,1B).

Figure 1 Sex-stratified analysis on the global burden of GBTC attributable to an elevated BMI in older adults. Comparison of (A) age-standardized death and DALYs rates and (B) absolute number of deaths and DALYs attributable to an elevated BMI stratified by gender in 2021; (C) trends in age-standardized death rates and DALY rates, and (D) temporal trends in the absolute number of deaths and DALYs attributable to an elevated BMI from 1990–2021. BMI, body mass index; DALYs, disability-adjusted life years.

Between 1990 and 2021, deaths increased by 169.7% in men and 84.1% in women, whereas DALYs increased by 152% in men and 77.6% in women. However, over the same period, the ASDR increased by 38.1% and ASDALYs increased by 12.2% in male patients, whereas the ASDR decreased by 15.8% and ASDALYs decreased by 18.7% in female patients (Figure 1C,1D).

Global burden of GBTC attributable to an elevated BMI in older adults: an age-stratified analysis

GBTC ASDR and ASDALY due to elevated BMI continued to increase with advancing age (Figure 2A,2B). The number of deaths increased with age, peaking in the 70–74 years age group (Table 1), and the number of DALYs increased with age, peaking in the 65–69 years age group (Table 2). From 1990 to 2021, the absolute number of deaths and DALY cases increased across all age groups, and the ASRs generally declined for most groups, except for the 90–94 and ≥95 years age groups, in which the ASRs exhibited an upward trend (Figure 2C,2D).

Figure 2 Age-stratified analysis on the global burden of GBTC attributable to an elevated BMI in older adults. (A) Age-standardized death rates and DALYs rates attributable to an elevated BMI by age subgroup in 2021, and (B) absolute number of deaths and DALYs. (C) Trends in age-standardized death rates and DALY rates attributable to an elevated BMI across age subgroups from 1990–2021, and (D) temporal trends in the absolute number of deaths and DALYs. BMI, body mass index; DALY, disability-adjusted life years.

Global deaths and DALY burden of elevated BMI-attributed GBTC in older adults: an SDI-based analysis

In 2021, the numbers of deaths (n=5,991; 95% UI: 3,378–7,177; Table 1) and DALYs (104,300; 95% UI: 39,349–79,377; Table 2) reported by countries with a high SDI were highest (Figure 3A,3B).

Figure 3 SDI-based analysis on global deaths and DALY burden of elevated BMI-attributed GBTC in older adults. (A) Age-standardized deaths rates and DALYs rates attributable to an elevated BMI across different SDI subgroups in 2021, and (B) absolute number of deaths and DALYs. (C) Trends in age-standardized deaths rates and DALYs attributable to an elevated BMI across SDI subgroups from 1990–2021, and (D) temporal trends in the absolute number of deaths and DALYs. BMI, body mass index; DALYs, disability-adjusted life years; SDI, socio-demographic index.

However, between 1990 and 2021, the largest relative increases in deaths (+325%) and DALYs (+317%) occurred in countries with low and medium SDIs. The largest increases in ASDR (+78.3%) and ASDALY (+74.1%) occurred in low- and middle-income areas (Figure 3C,3D).

Global deaths and DALY burden of elevated BMI-attributable GBTC in older adults: a GBD region-based analysis

Among the 54 regions defined in the GBD study, Asia reported the highest number of GBTC-related deaths (9,114; 95% UI: 5,945–13,042) and DALYs (184,559; 95% UI: 115,726–263,289) due to an elevated BMI among older people. In contrast, Oceania recorded the lowest number of GBTC-related deaths, with 4 deaths (95% UI: 3–6) and 103 DALYs (95% UI: 62–148; Tables S1,S2).

South Latin America ranked highest for deaths (4.62; 95% UI: 3.11–6.46) and DALYs (95.09; 95% UI: 64.02–131.5) with respect to ASRs, while West Africa had the lowest ASRs with a death rate of 0.03 (95% UI: 0.02–0.04) and a DALY rate of 0.62 (95% UI: 0.36–0.91; Tables S1,S2).

Hierarchical cluster analysis was used to cluster the areas with similar disease burden trends. The analysis revealed that GBTC-associated deaths and DALYs significantly increased from 1990 to 2021 based on the EAPC in southern Latin America, Latin American Caribbean, Central Europe, Central Asia (World Bank region), Central Latin America, and Western Europe. In marked contrast, Eastern Europe, Andean Latin America, Tropical Latin America, the high-income Commonwealth, high-income Asia-Pacific, Central Asia, North America, the Caribbean, high-income North America, Australasia, the broader European region, high-income World Bank countries, and advanced health systems had significant declines in deaths and DALYs (Figure 4).

Figure 4 Cluster analysis of EAPC in age-standardized deaths rates and DALYs rates attributable to an elevated BMI across GBD regions from 1990–2021. BMI, body mass index; DALYs, disability-adjusted life years; EAPC, estimated annual percentage change; GBD, Global Burden of Disease.

Global burden of elevated BMI-attributed deaths and DALYs for GBTC in older adults: a country-level analysis

The GBTC burden due to elevated BMI in older populations exhibits substantial global geographic variation. In 2021, Chile recorded the highest ASDR at 7.79 per 100,000 (95% UI: 5.26–11.02), followed by Bolivia [4.29 per 100,000 (95% UI: 2.35–6.84)] and the Czech [4.18 per 100,000 (95% UI: 2.69–6.01)]. Similarly, Chile had the highest ADALYS at 160.9 per 100,000 (95% UI: 108.79–224.78) with Bolivia [96.46 per 100,000 (95% UI: 51.87–155.72)] and Libya [84.98 per 100,000 (95% UI: 50.58-128.17)] ranking second and third, respectively. Gambia had one of the lowest ASRs for death [0 per 100,000 (95% UI: 0–0)] and DALYs [0 per 100,000 (95% UI: 0–0)] (Figure 5A,5B; Tables S1,S2).

Figure 5 Age-standardized deaths rates (A) and DALYs (B) rates attributable to an elevated BMI across different country/region subgroups in 2021, (C) and (D) absolute number of deaths and DALYs. BMI, body mass index; DALYs, disability-adjusted life years.

China had the highest number of GBTC-related deaths in 2021 (n=3,573; 95% UI: 2,007–5,296), followed by Japan (n=1,724; 95% UI: 1,083–2,465) and India (n=1,494; 95% UI: 889–2,088). China also recorded the highest number of DALYs (n=75,029; 95% UI: 42,272–111,152), followed by India and Japan (Figure 5C,5D; Tables S1,S2).

Iran had the most pronounced increase in deaths (727.3%) from 1990–2021, followed by India and the United Arab Emirates, whereas the United Arab Emirates exhibited the greatest increase in DALYs (688.6%), followed by Ghana and Iran (Tables S1,S2). Hungary experienced the largest decrease in deaths (36.3%), followed by Turkmenistan and Austria, and the largest decrease in DALYs (38.5%), followed by Austria and Turkmenistan (Tables S1,S2). Cape Verde had the greatest increase in deaths and DALYs (deaths: EAPC =4.91, 95% UI: 4.22–5.85; DALYs: EAPC =4.91, 95% UI: 3.98–5.85), followed by Iran. In contrast, Turkmenistan had the largest decrease (deaths: EAPC =−5.06, 95% UI: −6.21 to −3.9; DALYs: EAPC =−4.99, 95% UI: −6.18 to −3.78), followed by Sri Lanka (Tables S1,S2).

Projection analysis of deaths and DALY burden attributable to an elevated BMI for GBTC in older adults

An ARIMA model was used to predict the number of cases and the corresponding ASRs of these cancers for the period 2022–2050, based on GBTC data due to an elevated BMI in the elderly population from 1990 to 2021. The number of GBTC deaths related to an elevated BMI is projected to be 87.5% higher for males and 86.4% higher for females by 2050 compared to 2021. DALYs due to an elevated BMI were also projected to increase by 87.2% for men and 90.5% for women. It is projected that by 2050, the GBTC disease burden due to an elevated BMI among older populations will vary by sex, with ASDR and ADALYs increasing by 15.6% and 9.5%, respectively, in men, while the ASDR is predicted to decrease by 28.0% and DALYs by 9.5% in women. The ASDR and ADALYs for men were predicted to increase by 15.6% and 9.5%, respectively, whereas for women, the ASDR was predicted to decrease by 28.0% and ADALYs increased by 9.5% (Figure 6A,6B; Table S3).

Figure 6 Projected trends in the global burden of disease attributable to an elevated BMI across gender subgroups over the next 28 years [2022–2050] based on ARIMA modeling, including (A) age-standardized death rates and DALYs rates, and (B) absolute numbers of deaths and DALYs. ARIMA, autoregressive integrated moving average; BMI, body mass index; DALYs, disability-adjusted life years.

Discussion

This study examined the GBTC burden due to elevated BMI in the elderly population between 1990 and 2021. In 2021, there were 17,976 deaths and 360,029 DALYs related to GBTC due to elevated BMI among the older groups. The increase in deaths and DALYs over the past 31 years has been 110.3% and 101.3% per cent, respectively, compared with 1990. Global population aging and a significant increase in obesity rates over the past three decades are the main reasons for the significant increase in the disease burden (9,22). However, despite the increasing number and burden of cases, ASDR and ASDALY have shown a slight decline, especially in economically developed regions. This result is consistent with the findings reported by Hu et al. (10). This trend can be attributed to advances in medical technology, particularly the widespread adoption of early diagnostic techniques (e.g., biliary brushing and choledochoscopy), minimally invasive surgical methods, and the optimization of integrated oncology treatments, like adjuvant treatment, molecular therapy, and targeted therapy (23-25). These advances have effectively reduced postoperative complications and improved patient outcomes (23-25).

Deaths and DALYs increased progressively with age based on the age subgroup analysis, peaking at 70–74 and 65–69 years, respectively. Various tumors have been shown to be associated with elevated BMI (26). The cumulative effects of a chronically elevated BMI in older adults are particularly pronounced because persistent obesity significantly increases the risk of chronic inflammation, metabolic abnormalities, and gallstones, all of which are major causative factors for biliary tract tumors (26,27). Therefore, early screening and intervention for elevated BMI and metabolic syndrome in older adults with strengthened obesity management and biliary health monitoring are of critical public health significance.

Sex analysis indicated that death and DALYs were higher in females than males. Most older women experience declining estrogen levels (28). Estrogen exerts multifaceted regulatory effects on fat metabolism, glucose utilization, and inflammatory responses through estrogen receptors, which contribute to reduced tumor susceptibility (29). However, the decline in estrogen levels after menopause diminishes the protective effects and estrogen imbalance is recognized as a potential mechanism underlying gallstone formation (30). The interplay of these risk factors further elevates the risk of GBTC among older women. Hu et al. (10) reported that women are more prone to GBTC than men across all age groups. In the current study, ASDR and ASDALY continued to increase in men between 1990 and 2021, whereas a decreasing trend was observed in women. The results herein are consistent with the study by Zhan et al. (9). This gender disparity may be attributed to greater participation among women in health screenings and routine physical exams, particularly women >55 years of age, enabling early detection and intervention in conditions, such as GBTC, thereby reducing deaths and disease burden (31). The implementation of targeted screening and early detection for GBTC is especially important for at-risk populations, particularly individuals ≥55 years of age with an elevated BMI, as well as individuals with co-morbidities, such as gallstones and chronic biliary inflammation. These individuals should be prioritized for early screening to facilitate timely detection of potential risks and enable prompt intervention.

Regional analyses have shown that trends in GBTC burden related to elevated BMI varied across GBD regions over the past three decades. Countries with a high SDI facilitate a downward trend in GBTC burden through advanced medical resources and early screening measures (10,32). In addition, early cancer screening and advanced healthcare resources are generally limited in countries with a low and middle SDI, often resulting in late-stage diagnosis of GBTC (10,32). This delayed diagnosis contributes to poor treatment outcomes, leading to a significant increase in deaths and disease burden. For example, South Latin America and Central Europe have experienced substantial increases in deaths and DALYs, which are primarily attributed to dietary shifts that accompany economic development. This shift has led to a greater consumption of high-fat and high-sugar foods, contributing to significant increases in obesity rates and consequently increasing the incidence and deaths associated with GBTC. In contrast, Eastern Europe and North America have experienced a decline in the burden of these cancers, largely due to obesity prevention and control initiatives such as promoting healthy diets and encouraging exercise. These measures have helped maintain healthier BMI levels, significantly reducing the obesity-related cancer burden. These findings underscore the critical role of primary prevention in metabolic health and effective public health policies in mitigating the risk of obesity-related diseases (33).

At the national level, Chile has reported the highest ASDR and ASDALY for GBTC, primarily because of a rapid increase in obesity rates, dietary shifts, and limited healthcare resources (34). Chile is reported to have one of the highest obesity rates in Latin America, with approximately 75% of adults classified as overweight or obese (35). Additionally, the incidence of gallbladder cancer is particularly high among indigenous groups in the Andean region of Chile (36). This phenomenon is believed to be closely associated with the high prevalence of gallstones, traditional dietary habits, and genetic susceptibility. China has the highest absolute number of deaths and DALYs, primarily because of its large population, rapid aging, and rising prevalence of obesity (10,22). In contrast, Hungary has experienced a significant reduction in deaths and DALYs, primarily owing to healthcare system modernization and effective public health policies targeting tobacco control, weight reduction, and healthy diet promotion (37).

The global burden of GBTC due to elevated BMI is projected to nearly double the number of deaths and DALYs by 2050 compared to the 2021 levels. Notably, while ASDR and ASDALY for women are projected to decline, they ASDR and ASDALY are projected to increase for men, highlighting the disproportionate impact of obesity on men and the desirability of targeted interventions. Furthermore, the burden is expected to escalate rapidly in regions with a low to middle SDI, where efforts to prevent obesity and detect cancer early remain insufficient (32,38). Addressing these trends will require comprehensive public health strategies focused on promoting healthy dietary habits, increasing physical activity, and overcoming barriers to effective weight management, particularly among older groups (26,27). Expanding access to diagnostic services for high-risk groups, including individuals with gallstones or metabolic syndrome, and strengthening healthcare infrastructure in resource-limited regions are also critical for timely detection and effective treatment of GBTC (39).

This study provides an overview of the GBD and trends in GBTC related to elevated BMI in the elderly population. However, there are several limitations in this study. First, although data were drawn from multiple sources to estimate GBTC incidence, including vital registration systems, verbal autopsies, and cancer registries, data coverage remains limited or unavailable for some regions. In low-SDI regions, this modeling can introduce significant uncertainty, potentially conflating primary liver cancer with gallbladder cancer. This scarcity may have somewhat affected the accuracy of the assessment (40). Second, the four subtypes of biliary tract cancer (gallbladder cancer, intrahepatic cholangiocarcinoma, hilar cholangiocarcinoma, and distal cholangiocarcinoma) exhibit significant differences in incidence trends, risk factors, and geographic distribution (41). However, the GBD estimates did not anatomically stratify data for these distinct subtypes. Future studies should incorporate differential analyses of these subtypes to more accurately capture the unique epidemiological patterns and risk profiles associated with each subtype. Finally, in older age groups, elevated BMI is often closely associated with coexisting conditions such as diabetes and fatty liver disease, which can be potential risk factors for the burden of GBTC. Consequently, when analyzing the independent effect of BMI on biliary tract cancer in individuals aged >55 years, the presence of these confounding factors may impact the interpretation of the results (11,12).

Conclusions

Over the past 32 years, the GBTC burden due to elevated BMI had drastically increased globally among older people. This disease burden remained particularly high among women and in regions with a high SDI. However, the increasing burden trend was more pronounced and unfavorable among men and in regions with low-to-moderate SDI. Predictions indicate that this burden will likely continue to increase through 2050, underscoring the importance of monitoring these trends during the ongoing growth of global obesity rates and aging populations. The findings herein provide a scientific basis for policymakers to develop targeted public health strategies that address modifiable risk factors and curb rising GBTC burden.

Acknowledgments

None.

Footnote

Peer Review File: Available at https://jgo.amegroups.com/article/view/10.21037/jgo-2025-aw-915/prf

Funding: This study was supported by Shanghai Science and Technology Innovation Action Plan (No. 24QA2711900).

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jgo.amegroups.com/article/view/10.21037/jgo-2025-aw-915/coif). P.C. reports this study was supported by Shanghai Science and Technology Innovation Action Plan (No. 24QA2711900). The other 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.

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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Cite this article as: Chen P, Qin W, Hu B. Global burden landscape (1990–2021) of gallbladder and biliary tract cancer attributable to high body mass index in older adults and a projection to 2050. J Gastrointest Oncol 2026;17(3):171. doi: 10.21037/jgo-2025-aw-915

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