Burden of pancreatic cancer in Iran: an analysis of Global Burden of Disease 2021

Abstract

Aim:

To assess national and provincial trends in pancreatic cancer (PC) incidence, mortality, and mortality-to-incidence ratio (MIR) in Iran (1990–2021) using Global Burden of Disease (GBD) 2021 data.

Background:

PC is highly lethal, and recent burden estimates for Iran are limited.

Methods:

Age-standardized and age-specific incidence and mortality rates were obtained from the GBD Results Tool; MIR was calculated. Joinpoint regression was used to estimate average annual percentage change (AAPC) overall, by sex, and in adults aged ≥55 years.

Results:

From 1990 to 2021, age-standardized incidence and mortality increased by 80% (1.98 to 3.57 per 100,000) and 73% (2.12 to 3.65 per 100,000), respectively, while the MIR declined slightly (1.07 to 1.02) but remained above 1. Among adults ≥55 years, incidence and mortality nearly doubled (8.31 to 16.84 and 8.73 to 17.38 per 100,000, respectively), with minor MIR reductions (1.05 to 1.03). Joinpoint regression confirmed significant national increases in incidence (AAPC:1.88%) and mortality (AAPC:1.73%), alongside a modest decline in MIR (AAPC:−0.14%). Provincially, all regions exhibited rising age-standardized incidence and mortality, most steeply in Ilam and the lowest in Tehran. MIR generally declined, notably in Tehran, Lorestan, and Chaharmahal and Bakhtiari, though slight increases occurred in South/North Khorasan, Markazi, and Sistan and Baluchestan.

Conclusion:

PC burden in Iran has increased subs`tantially over the past three decades, especially among older adults and in certain provinces. Persistently high MIR indicates late diagnosis and poor survival, highlighting the need to strengthen cancer registries, improve early detection and diagnostic capacity, and address modifiable risk factors.

Introduction

Pancreatic cancer (PC) is a complex disease and one of the deadliest cancers worldwide (1). In 2021, its global age-standardized incidence and mortality rates were estimated at 5.96 and 5.95 cases per 100,000 population per year, respectively, with a mortality-to-incidence ratio (MIR) of 0.99 (2). According to GLOBOCAN 2022, PC ranks twelfth in global cancer incidence and sixth in cancer-related mortality, contributing to nearly 5% of all cancer deaths worldwide (3). In Iran, the latest data from the National Cancer Registry Program, reported in 2017, showed an age-standardized incidence rate of 3.45 per 100,000 population (4). However, no recent national-level estimates are available regarding the mortality rate of PC in Iran. Nonetheless, several earlier or region-specific studies have examined mortality patterns over short periods, reporting variable trends in both incidence and mortality (5-8).

From 1990 to 2021, the global burden of PC rose sharply, with the number of new cases increasing from about 208,000 to 508,500 and deaths rising from 211,600 to 505,700 (2). This upward trend has also been seen in most Asian countries (9, 10), with the notable exception of some East Asian nations such as Japan and South Korea, where rates have remained stable or declined (11). Several factors contribute to this rise, including high smoking rates (12), increasing obesity and diabetes (13, 14), and lifestyle changes toward Western-style diets (15). PC Mortality linked to smoking rises with the Sociodemographic Index (SDI), a composite indicator of income per capita, educational attainment, and fertility rate, but declines when SDI exceeds 0.8 (16). Higher educational attainment and improved healthcare may also lower risk (17, 18). In Iran, the limited available evidence also indicates variable short-term trends in incidence and mortality, with smoking, aging, and lifestyle changes identified as the main contributing factors (4, 19).

Strengthening cancer registries is crucial for developing effective cancer control programs that can enhance patient outcomes and decrease mortality rates. When a country or province shows a high MIR, it may signal that many cases are being diagnosed too late or that treatment options are limited (3, 20). This makes it crucial to regularly track incidence, mortality, and MIR to inform health policies, enhance services, and ensure that resources are utilized in the most effective manner. In Iran, however, there have been only few studies that examine the current incidence, mortality, or MIR of PC, and recent trends have not been comprehensively evaluated (19, 21). The lack of information is even more pronounced at the provincial level, where data on the scale and direction of these measures are almost nonexistent. This study aimed to fill these gaps by analyzing national and provincial trends in pancreatic cancer incidence, mortality, and MIR in Iran from 1990 to 2021, using data from the Global Burden of Disease (GBD) study.

Methods

Study data

This study used publicly available secondary data from the GBD 2021 project, which is an international effort led by the Institute for Health Metrics and Evaluation (IHME) that compiles comparable health data from over 200 countries and territories (22, 23). The GBD estimates disease burden through standardized modeling approaches using multiple national and international data sources. For this study, we focused on assessing the burden of PC in Iran between 1990 and 2021. All data were obtained from the Global Health Data Exchange (GHDx) via the GBD Results Tool (24).

Variables

This study focused on three key indicators of PC: incidence, mortality, and the MIR (25). The incidence rate is the number of new PC cases per 100,000 population in a year, adjusted for age so that results can be compared across different populations and time periods. The mortality rate is the number of deaths from PC per 100,000 population per year, adjusted for age. The MIR is calculated by dividing the mortality rate by the incidence rate, showing how deadly the disease is in relation to how often it occurs:

MIR = Mortality rate / Incidence rate

To measure the uncertainty around MIR, we calculated the standard error (SE) using the upper and lower bounds of the 95% uncertainty intervals (UIs) for both incidence and mortality. This was based on a log-normal approximation, assuming the two measures are independent. The formula used was:

SE _MIR = MIR × SQRT(((Upper _Mortality – Lower _Mortality) / (2 × 1.96 × Mortality))² + ((Upper _Incidence – Lower _Incidence) / (2 × 1.96 × Incidence))²)

“Upper” and “Lower” are the upper and lower limits of the 95% uncertainty interval, and 1.96 is the Z-score for a 95% confidence level. We examined these indicators for the whole country, by sex, by province, and by age group. A special focus was placed on people aged 55 years and older. It should be noted that the calculation of MIR uncertainty assumes statistical independence between incidence and mortality estimates. However, as both indicators may be derived from shared data sources within the GBD framework, some degree of correlation or systematic bias may exist. This assumption was retained for consistency with previous GBD-based studies.

Statistical analysis

Descriptive statistics

To describe how the burden of PC changed over time, we calculated the percent change in incidence, mortality, and MIR from 1990 to 2021. This was achieved by subtracting the 1990 value from the 2021 value, then dividing the result by the 1990 value, and finally multiplying by 100 to obtain a percentage.

Joinpoint regression

To assess temporal trends in age-standardized burden indicators of PC, joinpoint regression modeling was applied. This statistical method identifies significant changes in trend patterns by fitting segmented linear regressions to annual data. Percent changes in incidence, mortality, and MIR from 1990 to 2021 were calculated to capture descriptive variations across provinces, sexes, and time periods. The joinpoint model estimates points of inflection, or “joinpoints,” where a statistically significant change in slope occurs. The general model used was:

yᵢ = β₀ + β₁tᵢ + γ₁(tᵢ − τ₁) + … + γₖ(tᵢ − τₖ) + εᵢ,

where yᵢ represents the burden metric at time tᵢ, β and γ are regression coefficients, τₖ indicates the timing of joinpoints, and εᵢ is the random error term. For each segment, the annual percentage change (APC) was derived using the formula:

APC = 100 × [exp(β₁ + γ₁ + γ₂ + ... + γⱼ) − 1].

The average annual percentage change (AAPC) is then computed as a time-weighted summary of all APCs across segments (26). Ninety-five percent confidence intervals (CIs) were calculated to assess the statistical significance of each trend. All joinpoint analyses were performed using the Joinpoint Regression Program version 5.2.0 (National Cancer Institute, USA) (27).

Results

Descriptive national trends in pancreatic cancer burden, 1990–2021

Between 1990 and 2021, the age-standardized incidence and mortality rates of PC in Iran rose by 80.42% (from 1.98 to 3.57 per 100,000) and 72.72% (from 2.12 to 3.65), respectively, while the MIR declined by 4.26% (from 1.07 to 1.02), as shown in Table 1. Among individuals aged ≥55 years, incidence and mortality increased relatively by 102.73% and 99.19%, respectively, with a 1.75% decline in MIR. These trends were consistent across both sexes.

Table 1.

Trends in age-standardized and age-specific (≥55 Years) rates of PC mortality, incidence, and MIR per 100,000 population in Iran, 1990–2021

Population Group	Measure	Sex	Year		Percent Change
			1990	2021
Age-standardized	Mortality	Both	1.98	3.57	80.42
		Female	1.62	2.66	64.29
		Male	2.33	4.49	93.13
	Incidence	Both	2.12	3.65	72.72
		Female	1.77	2.84	61.08
		Male	1.98	3.57	80.42
	MIR	Both	1.07	1.02	-4.26
		Female	1.09	1.07	-1.96
		Male	1.06	1.00	-5.58
Aged ≥55 Years	Mortality	Both	8.31	16.84	102.73
		Female	6.94	12.74	83.42
		Male	9.49	21.01	121.42
	Incidence	Both	8.73	17.38	99.19
		Female	7.44	13.62	83.17
		Male	9.85	21.21	115.37
	MIR	Both	1.05	1.03	-1.75
		Female	1.07	1.07	-0.14
		Male	1.04	1.01	-2.73

Note: All values represent rates per 100,000 population unless otherwise specified. Age-standardized and ≥55-year rates were estimated for pancreatic cancer in Iran across three key measures: incidence, mortality, and the mortality-to-incidence ratio (MIR). Rates for 1990 and 2021 were reported, and the percent change between these years was calculated as: Percent change = [(Value in 2021 − Value in 1990) / Value in 1990] × 100. Percentage changes were computed using full-precision values (e.g., MIR for females aged ≥55 years: 1.0708 in 1990 and 1.0693 in 2021, yielding −0.14%) but rounded to two decimal places for presentation consistency. All numerical values have been standardized to two decimal places across the main and supplementary tables.

Descriptive provincial trends in pancreatic cancer burden, 1990–2021

Figure 1 shows that the spatial distribution of incidence and mortality has remained consistent across provinces each year from 1990 to 2021, with Alborz, Qom, Tehran, and Yazd reporting the highest rates and Bushehr, Chaharmahal and Bakhtiari, Hormozgan, and Sistan and Baluchestan showing the lowest. In contrast, MIR showed a different pattern, with the lowest values observed in Chaharmahal and Bakhtiari, Mazandaran, and Tehran, whereas East and West Azerbaijan recorded the highest. Among adults aged 55 years or older, MIR varied more widely across provinces in each year. Notably, for both age-standardized and age-specific groups, all MIR values remained above 1, indicating that the estimated mortality rate exceeded the incidence rate.

Figure 1.

Age-standardized incidence, mortality (per 100,000 population), and MIR of PC across Iranian provinces from 1990 to 2021, stratified by total population (A–C) and individuals aged 55 years and older (D–F) [Values were z-score standardized by year across provinces to emphasize relative spatial variation in each year. Green shades indicate values below the national mean for that year; purple shades indicate values above it.]

At the provincial level, Ilam showed the highest relative increases in PC incidence (166.65%) and mortality (157.51%) from 1990 to 2021, while Tehran had the lowest (36.01% and 29.34%, respectively). MIR declined in all provinces, with the largest decrease in Chaharmahal and Bakhtiari (−5.52%) and the smallest in Sistan and Baluchestan (−2.08%). Among adults aged 55 years and older, Alborz had the lowest increases in incidence (44.51%) and mortality (33.91%), whereas Ilam again recorded the highest increases (190.55% and 184.31%). In this group, MIR declined most in Alborz (−3.18%) but increased in South Khorasan (0.19%), North Khorasan (0.56%), Markazi (0.58%), and Sistan and Baluchestan (0.94%). Full details are provided in Supplementary Tables S1 and S2.

Modeled national trends based on Joinpoint analysis, 1990–2021

In the next step, joinpoint regression analysis was conducted to assess temporal trends in the PC burden. As presented in Table 2, results revealed significant upward trends in the age-standardized incidence and mortality rates of PC in Iran, with AAPCs of 1.88% (95% CI: 1.81–1.94) and 1.73% (95% CI: 1.66–1.79), respectively. MIR showed a significant decline (AAPC: −0.14%; 95% CI: −0.14 to −0.14). Among individuals aged 55 years or older, increases were more pronounced, with incidence and mortality rising at AAPCs of 2.27% (95% CI: 2.21–2.32) and 2.22% (95% CI: 2.16–2.27), respectively. MIR in this group declined modestly but significantly (AAPC: −0.06%; 95% CI: −0.06 to −0.05). Figure 2 illustrates segmented increases in incidence and mortality, along with a gradual decline in MIR, with steeper trends observed among those aged 55 years and older, reflecting faster increases in incidence and mortality, as well as slightly sharper declines in MIR.

Table 2.

AAPC and Joinpoint Regression Results for Age-Standardized and Age-Specific (≥55 years) Rates of PC Incidence, Mortality, and MIR per 100,000 Population in Iran, 1990–2021, by Sex

Population Group	Measure	Sex	No. of Joinpoints	AAPC (95% CI)	P-value
Age Standardized	Incidence	Both	6	1.88* (1.81, 1.94)	< 0.001
		Female	4	1.57* (1.51, 1.63)	< 0.001
		Male	6	2.09* (2.02, 2.17)	< 0.001
	Mortality	Both	6	1.73* (1.66, 1.79)	< 0.001
		Female	5	1.51* (1.45, 1.56)	< 0.001
		Male	6	1.91* (1.84, 1.98)	< 0.001
	MIR	Both	6	-0.14* (-0.14, -0.14)	< 0.001
		Female	4	-0.06* (-0.07, -0.06)	< 0.001
		Male	4	-0.19* (-0.19, -0.18)	< 0.001
Aged ≥55 Years	Incidence	Both	6	2.27* (2.21, 2.32)	< 0.001
		Female	6	1.94* (1.89, 1.98)	< 0.001
		Male	6	2.56* (2.49, 2.62)	< 0.001
	Mortality	Both	6	2.22* (2.16, 2.27)	< 0.001
		Female	6	1.95* (1.9, 1.99)	< 0.001
		Male	6	2.48* (2.41, 2.54)	< 0.001
	MIR	Both	6	-0.06* (-0.06, -0.05)	< 0.001
		Female	2	-0.01 (-0.01, 0)	0.070
		Male	6	-0.09* (-0.09, -0.08)	< 0.001

Note: Joinpoint regression analysis was used to identify significant temporal trends. AAPC values marked with an asterisk (*) indicate statistical significance at p < 0.05.*. Estimates were calculated separately for the total population and individuals aged ≥55 years. AAPC: average annual percentage change; CI: confidence interval; MIR: mortality-to-incidence ratio.

Figure 2.

Joinpoint regression analysis of PC incidence, mortality, and MIR in Iran, 1990–2021. [Panels A–C display age-standardized rates, and panels D–F show corresponding age-specific rates among individuals aged ≥55 years. Trends are presented with the annual percentage change (APC) for each segment identified by the Joinpoint regression model.]

Modeled provincial trends based on Joinpoint analysis, 1990–2021

Figure 3 illustrates the spatial variation in AAPCs of age-standardized measures at the provincial level using joinpoint regression. All provinces showed positive AAPCs for incidence and mortality, with the steepest increases in Ilam and among the lowest in Tehran. In contrast, MIR declined across all provinces, most notably in Tehran, Lorestan, Chaharmahal and Bakhtiari, and Kohgiluyeh and Boyer-Ahmad. These declining trends were more pronounced in males than in females. As depicted in Figure 4 for individuals aged ≥55 years, the highest AAPCs were observed in Ilam, Fars, and Bushehr. At the same time, the lowest were seen in Tehran, Alborz, Mazandaran, Qom, Khuzestan, and Hormozgan. For MIR, central provinces generally showed declining trends, a pattern that was evident across nearly all provinces among males. Detailed AAPC values are provided in Supplementary Tables S3 and S4.

Figure 3.

AAPC-based trends in age-standardized incidence, mortality, and MIR of PC across Iranian provinces by sex, 1990–2021. [(A) Incidence in males, (B) Incidence in females, (C) Mortality in males, (D) Mortality in females, (E) MIR in males, (F) MIR in females.]

Figure 4.

AAPC-based trends in incidence, mortality, and MIR of PC among adults aged ≥55 years across Iranian provinces by sex, 1990–2021. [(A) Incidence AAPCs in ≥55 males, (B) Incidence AAPCs in ≥55 females, (C) Mortality AAPCs in ≥55 males, (D) Mortality AAPCs in ≥55 females, (E) MIR AAPCs in ≥55 males, (F) MIR AAPCs in ≥55 females.)]

Discussion

Between 1990 and 2021, the age-standardized incidence and mortality rates of PC in Iran increased by over 70%, highlighting a substantial rise in disease burden over three decades. In parallel, age-specific rates among individuals aged 55 years and older nearly doubled, reflecting the disproportionate impact of PC on older populations. During the same period, the MIR, which reflects the number of deaths relative to new cases, showed an approximately 2.5-fold larger absolute reduction in the total population than in the ≥55 age group, suggesting possible improvements in early detection or access to care among the broader population. At the national level, MIR remained above 1 throughout the study period, indicating that the number of deaths consistently exceeded the number of new cases per 100,000 persons. Increases in both incidence and mortality, as well as the decline in MIR, were more pronounced in males than in females, possibly due to differences in risk factors, health-seeking behavior, or access to healthcare. At the provincial level, Ilam exhibited the steepest relative increases in age-standardized and age-specific incidence and mortality, whereas Tehran showed the smallest increases. In absolute terms, Tehran’s rates remained among the highest throughout the study period, highlighting notable regional disparities in PC burden. MIR also remained above 1 in nearly all provinces and showed a declining trend over time. Joinpoint regression analysis confirmed persistent upward trends in both age-standardized and age-specific incidence and mortality rates across Iran, reflecting a continuous rise in the burden of PC. Although MIR declined modestly at the national level, particularly among males, it remained above 1 in almost all provinces, indicating ongoing challenges in early detection and survival improvement. Provinces such as Ilam showed the steepest increases, whereas Tehran exhibited the lowest AAPCs, underscoring significant regional disparities that call for targeted public health interventions.

Our findings revealed an upward national trend in the age-standardized incidence rate of PC in Iran, consistent with the results of Nejadghaderi et al., who reported a substantial increase in PC incidence in Middle East and North Africa (MENA) countries (28). In our analysis, this increasing trend was more pronounced among individuals aged 55 years or older, aligning with the findings of Rashid et al., who reported an AAPC of 1.91% between 1990 and 2021 in the MENA region, which is closely comparable to our estimates (29). Furthermore, we observed a higher burden of PC among males than females, a pattern also reported by Elwali et al. in their study, which was based on the WHO International Agency for Research on Cancer (IARC) Global Cancer Observatory data for Saudi Arabia (30). However, the number of studies from the MENA region that allow direct comparison with our findings remains limited. This finding is consistent with the observations of Nassereldine et al., who highlighted significant gaps and limitations in PC research across most MENA countries, including Iran (Nassereldine et al.,). This pattern is concerning and underscores the need to identify the underlying drivers of this increase and to develop strategies to mitigate it. Evidence suggests that controlling well-established modifiable risk factors is essential. Priority interventions include reducing cigarette smoking (12, 32, 33), particularly among individuals with diabetes (34), addressing obesity through targeted lifestyle and behavioral modifications (35), and promoting healthier dietary patterns with lower intake of high-fat foods (17, 35). Implementation of comprehensive, evidence-based public health programs targeting these risk factors could help slow, or potentially reverse, the rising incidence of PC in Iran and the broader MENA region.

Other findings of this study include the observed increasing trend in age-standardized incidence rates of PC in Iran. Although limited, existing studies have reported similar results. For example, Siri et al. documented a twofold increase in PC mortality in Iran between 1990 and 2017 (19), while Darbandi et al. reported that PC mortality ranking in Iran rose from 13th to 9th place between 1990 and 2019 (21). This upward trend may be attributable to higher smoking prevalence (36), population aging (12, 37), and lifestyle changes (19, 21, 38, 39). In a regional context, Nejadghaderi et al. found that in 2019, the highest age-standardized incidence rates of PC in the MENA were reported in the United Arab Emirates (17.6 per 100,000), Turkey (8.2), Qatar (8.1), Bahrain (7.6), and Libya (7.3), several of which are geographically close to Iran. These neighboring countries may share similar environmental exposures, lifestyle patterns, and healthcare system limitations, which could partly explain comparable regional trends rather than any direct effect of proximity itself (28). Additionally, the region's lack of advanced medical infrastructure for diagnosis and treatment significantly contributes to poor health outcomes (31, 40). Our study also revealed that mortality was higher both in absolute values and in the rate of increase among individuals aged ≥55 years, a finding consistently emphasized in previous studies (10, 41). This pattern may reflect age-related physiological decline and immunosenescence, which increase susceptibility to pancreatic cancer (42). Moreover, PC mortality was higher in men than in women, most likely reflecting higher smoking prevalence among men (43-45). These findings highlight that male smokers with diabetes may face a markedly increased risk of PC. Therefore, a logical first step would be to target this group through appropriate education and tailored interventions to control these risk factors, which, in any case, calls for a national policy.

One of the most challenging findings of this study was the MIR exceeding 1 in Iran, indicating that more deaths than new cases were recorded. This may reflect the rapid progression of pancreatic cancer, with some patients dying before diagnosis, as well as frequent late-stage detection due to the absence of specific tumor markers and non-specific early symptoms (19, 46, 47). These factors contribute to the cancer’s poor prognosis and the high MIR observed. Although the MIR trend shows a decline, particularly among men, this does not necessarily indicate improved survival; instead, it may reflect increased disease awareness and better access to diagnostic tools, resulting in higher reported incidence (48-51). A similar downward trend has been documented in most high-income countries, which is primarily attributed to higher Human Development Index (HDI) levels (52). In Iran, achieving similar progress will require improving diagnostic accuracy, implementing targeted screening for high-risk groups, enhancing public awareness, expanding diagnostic capacity, and ensuring timely referral and treatment.

In Iran, there have been few recent and comprehensive studies looking at how pancreatic cancer affects different provinces over time (32, 53, 54). This analysis addresses this data gap and highlights distinct regional disparities across the country. Certain provinces consistently demonstrate higher incidence and mortality rates, whereas others maintain comparatively lower levels. The overall trend in age-standardized incidence and mortality rates was positive, with comparatively smaller increases observed in Tehran. Although the geographic pattern of incidence and mortality has stayed mostly the same, the pattern for age-standardized MIR is more varied, suggesting differences in how quickly cases are detected, how easily people can get diagnosed, and the availability of treatment. In most provinces, the age-standardized MIR has declined, especially in men, but it is still above 1 everywhere, which means deaths still outnumber new cases and survival remains poor. Among people aged 55 and older, provinces in the center and south, such as Fars and Bushehr, have experienced some of the fastest increases in both incidence and mortality, highlighting an urgent need for targeted action. In this age group, MIR has been rising in provinces such as Markazi, Sistan and Baluchestan, as well as North and South Khorasan. This increase in MIR is visible among women in most provinces, especially in Markazi, while for men it is mainly limited to Sistan and Baluchestan and North Khorasan. These findings indicate that each province requires a tailored intervention strategy addressing its specific epidemiological and healthcare challenges. In high-burden areas, this entails strengthening early detection pathways, ensuring timely referral to appropriate specialists, enhancing community-level awareness of early symptoms, and prioritizing high-risk older adults in screening and treatment initiatives.

The principal strength of this study lies in its comprehensive evaluation of PC incidence, mortality, and MIR at both national and provincial levels, with annual estimates and temporal trends spanning from 1990 to 2021. To our knowledge, this represents the first such analysis in Iran, providing valuable insights into the suboptimal status of PC diagnosis and treatment nationwide. Nonetheless, several limitations should be acknowledged. First, the study relied on modeled estimates rather than directly measured data. Although these estimates were derived using robust and validated GBD methodologies, they may be affected by data quality limitations due to the absence of a fully comprehensive, population-based national cancer registry in Iran. Second, the GBD estimates are synthesized from multiple secondary data sources, which may introduce potential biases or uncertainties related to heterogeneity among sources. Third, as a descriptive ecological study, this analysis cannot establish causal relationships; the observed associations between temporal patterns and potential contributing factors such as aging, smoking, or lifestyle changes should be interpreted as suggestive rather than definitive. Finally, although the most recent data available at the time of analysis extended through 2021, any potential changes in incidence and mortality after that period were not captured. Despite these limitations, our findings underscore the urgent need to strengthen cancer surveillance systems, enhance data quality, and expand national cancer registry coverage to improve the accuracy and timeliness of future PC burden assessments in Iran.

Conclusion

Pancreatic cancer burden in Iran has grown markedly from 1990 to 2021, with both incidence and mortality increasing across all provinces. The persistently high mortality-to-incidence ratio (MIR >1) highlights the predominance of late diagnosis and limited survival improvement. Strengthening cancer registries, improving early diagnostic capacity, and addressing key modifiable risk factors such as smoking, obesity, and diabetes should be prioritized to curb the rising burden and reduce regional disparities in outcomes.

Ethics approval

The study protocol was reviewed and approved by the Research Ethics Committee of the Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran (Approval Code: IR.SBMU.RIGLD.REC.1404.028). All analyses were based on aggregated data from the GBD 2021 study, and no individual-level data were used.

Availability of data and materials

The datasets analyzed during the current study are publicly available from GBD Results Tool at:

• http://ghdx.healthdata.org/gbd-results-tool

• http://hdr.undp.org/en

Conflict of interests

There is no conflict of interest for authors of this article.