The Burden of Colorectal Cancer in Iran During 1995- 2019: Findings From the Global Burden of Disease Study

1.Introduction
Colorectal cancer (CRC), a malignancy affecting the colon and rectum, represents a significant global public health challenge. It is the third most commonly diagnosed cancer in men and the second in women, accounting for over 10% of all cancer cases worldwide [1]. According to GLOBOCAN projections, the global burden of CRC is expected to reach approximately 3.2 million cases by 2040 [2]. Each year, nearly one million deaths are attributed to CRC, with the highest mortality rates reported in Asia [3]. In 2019, the age-standardized mortality rate per 100,000 population was 17.41 in the Americas, 3.7 in Africa, 35.21 in Europe, and 12.31 in Asia [4].
In 2020, Hungary, Slovakia, Norway, the Netherlands, and Denmark reported the highest age-standardized incidence rates of CRC, with 45.3, 43.9, 41.9, 41.0, and 40.9 cases per 100,000 population, respectively. In contrast, the lowest incidence rates—fewer than 4 cases per 100,000—were observed in Guinea, Gambia, Bangladesh, Bhutan, and Burkina Faso [5]. While the incidence of CRC has stabilized or declined in many high-income countries—including Australia, New Zealand, the United States, and several Western European nations—it is increasing rapidly in numerous low- and middle-income countries, including Iran [6].
In Iran, CRC has shown a notable upward trend. It rose from being the 7th and 25th leading cause of disability-adjusted life years (DALYs) in men and women, respectively, in 1990, to the fourth leading cause for both sexes by 2017. CRC is currently the third most common cancer in Iranian men and the second in women. Correspondingly, CRC-related mortality has increased from 2.87 per 100,000 in the early 1990s to 6.8 per 100,000 in 2017 [7]. The estimated 5-year survival rate for CRC in Iran is 0.50 (0.56–0.44) in women and 0.44 (0.4–0.48) in men [8].
CRC imposes a considerable health and economic burden on the Iranian population. However, despite its rising impact, there remains a scarcity of comprehensive studies examining the long-term burden of CRC at the population level in Iran [9, 10]. In response, this study aims to assess the burden of CRC in Iran from 1995 to 2019 using data from the global burden of disease (GBD) study. Unlike previous Iranian studies that have focused primarily on incidence rates, aggregated cancer data, or regionally limited analyses, this research provides a nationwide, 25-year DALY-based evaluation of CRC. Moreover, it offers the first age- and sex-stratified national estimates of CRC burden over time.

2. Materials and Methods
2.1. Data sources
This study utilized two primary categories of data: CRC burden metrics and Iranian population statistics. CRC burden data included DALYs, years of life lost (YLLs), years lived with disability (YLDs), number of deaths, incidence, and prevalence. These data were retrospectively extracted from the GBD reports, published by the Institute for Health Metrics and Evaluation (IHME), covering the period from 1995 to 2019 [4]. Population data for Iran, stratified by sex and age group, were obtained from the World Bank Statistics and the Iranian Statistical Center.

2.2. Data analysis
This study represents a secondary analysis of GBD study results. Mortality and morbidity indicators were employed to evaluate the burden of CRC. Crude rates of mortality, incidence, and prevalence were reported, along with DALYs, YLLs, and YLDs, stratified by age group and sex for the years 1995–2019. Age groups were defined in accordance with the World Health Organization (WHO) and previous studies, including: <5 years, 5–14 years, 15–49 years, 50–69 years, and ≥70 years.
DALY, a composite measure developed by the WHO, was used to quantify and compare the burden of disease across populations and time periods. This metric is particularly useful in evaluating the impact of diseases and guiding health policy by incorporating both premature mortality (YLLs) and non-fatal health outcomes (YLDs). One DALY represents the loss of one year of healthy life due to illness, disability, or premature death [11].
Descriptive statistics included the number of cases and rates of incidence, prevalence, DALYs, YLLs, and YLDs, all stratified by age and sex. Analytical statistics were performed to assess significant differences in burden across demographic groups. Independent t-tests were used to compare means across age groups and sexes, while the Jonckheere-Terpstra test was applied to evaluate temporal trends. All statistical analyses were conducted using Stata version 14 (Stata Corp, College Station, TX, USA). A P<0.05 was considered statistically significant.

3. Results
Between 1995 and 2019, a total of 94,188 CRC-related deaths were recorded in Iran across both sexes, with a consistently higher incidence observed in males compared to females. Over this period, the incidence rate of CRC increased from 4.63 to 7.19 per 100,000 population. Similarly, the prevalence rate rose from 19.23 to 31.83 per 100,000 population for both sexes combined (Table 1).

Table 2 presents the total number of deaths and DALYs attributable to CRC in Iran, stratified by age group, for the period 1995–2019.

During this time, CRC accounted for an estimated 2,426,900 DALYs across all age groups, with males contributing 1,330,961 DALYs and females 1,095,938 DALYs. The total number of CRC-related deaths over the same period was 94,189.
Among females, total YLLs rose from 128,617 in 1995–1999 to 322,554 in 2015–2019, while males showed a rise from 156,008 to 398,242 over the same period. Similarly, YLDs increased from 2,506 to 7,525 among females and from 3,871 to 13,127 among males. Total DALYs increased markedly: in females, from 131,122 in 1995–1999 to 330,077 in 2015–2019; in males, from 159,876 to 411,369 during the same periods. Age-specific analysis showed the greatest burden among individuals aged 50 and older. The Jonckheere–Terpstra trend test confirmed a significant increasing trend in YLLs, YLDs, and DALYs across all age groups (P<0.001). Additionally, The Ona-way analysis of variance (ANOVA) shows a significant difference in the number of DALYs, YLLs and YLDs based on age groups (Table 3).

Figure 1 illustrates the rates of YLLs and DALYs per 100,000 population attributable to CRC, disaggregated by sex, from 1995 to 2019.

A marked increase in both indicators was observed in both males and females. Notably, the rate of DALYs per 100,000 population was consistently higher in males than in females throughout the entire period.

4. Discussion
According to the GBD study, there has been a marked increase in CRC-related epidemiological indicators in Iran between 1995 and 2019. Over this 25-year period, CRC accounted for more than 2.4 million DALYs and approximately 94,100 deaths across all age groups and both sexes. The incidence rate of CRC rose from 4.63 per 100,000 individuals in 1995–1999 to 10.85 per 100,000 in 2015–2019, while the prevalence rate increased from 19.32 to 49.45 per 100,000 individuals.
Our analysis revealed that the morbidity and mortality indicators for CRC in Iran have increased at a faster rate compared to some other countries. Specifically, CRC incidence in Iran increased approximately 2.72-fold, while the prevalence rose 3.05-fold over the study period. DALYs attributable to CRC increased 2.9-fold, and CRC-related deaths rose by a factor of 3.3. In 2019, CRC accounted for approximately 0.8% of total DALYs and 1.6% of all deaths in Iran. In contrast, DALYs attributable to CRC comprised 0.18%, 0.48%, 1.7%, and 2% of total DALYs in low, low-middle, high-middle, and high sociodemographic index (SDI) countries, respectively [4]. The GBD study also reported that among 204 countries, 157 experienced a doubling or more in CRC incidence, and 129 observed at least a doubling in CRC-related mortality between 1990 and 2019 [12]. Globally, CRC deaths surpassed 9.2 million by 2019, reflecting an increase of more than 109% since 1990 [13].
The greatest burden of CRC was observed in individuals aged 50–69 years, who accounted for approximately 45% of CRC-related DALYs and 38% of CRC deaths during the study period. Individuals aged 15–49 and those aged ≥70 years contributed 28% and 26% of DALYs, respectively. Notably, the highest proportion of deaths (47%) occurred in individuals aged 70 years and older. These findings are consistent with the established understanding of CRC as a disease strongly associated with aging. The risk of developing colorectal polyps—which may progress to malignancy if not detected and removed—increases substantially with age. The likelihood of adenomas advancing to CRC rises significantly after age 50, accompanied by an elevated risk of both CRC incidence and mortality [14]. However, the high burden of CRC in the 50–69 age group in Iran may also reflect demographic trends, including the expansion of the middle-aged population. Prior studies have shown that 35% of the increase in CRC burden from 1990 to 2013 was attributable to population growth, while 41.9% was due to changes in age structure [15].
Our findings also revealed a significantly higher burden of CRC in men compared to women across all measured indicators, including DALYs, incidence, prevalence, and mortality. This gender disparity became more pronounced with increasing age. These results are supported by prior research indicating that women have a lower lifetime risk of developing CRC and tend to present with distinct tumor characteristics at both clinical and molecular levels [6]. A meta-analysis confirmed that men have a significantly higher risk of developing advanced colorectal neoplasia and cancer, regardless of age [16]. Similarly, other studies reported a higher number of CRC cases and related deaths among men compared to women up to the age of 80–84 years [12]. A population-based study in China also highlighted significant gender disparities in CRC incidence [17]. Several biological and behavioral factors may contribute to this disparity. Men generally have higher levels of visceral adiposity and are more likely to engage in behaviors such as smoking and alcohol consumption, all of which are associated with increased CRC risk [18]. Conversely, endogenous estrogen exposure and the use of oral contraceptives in women have been shown to exert protective effects against CRC [19].
To the best of our knowledge, this study provides a comprehensive analysis of CRC epidemiological trends in Iran using GBD data spanning from 1995 to 2019. It offers important insights into the temporal evolution of CRC burden across age and sex groups, which may inform future public health strategies and resource allocation. Nevertheless, several limitations must be acknowledged. This study relied on secondary data from the GBD study, which may be subject to inherent limitations in data quality, completeness, and model-based estimations.

5. Conclusion 
CRC remains a major public health concern in Iran and globally. The predominance of YLLs in the total DALYs underscores the urgent need for effective preventive strategies, early detection, and widespread screening programs. Given the increasing burden observed in individuals aged 50–69 years, and the emerging trends in younger populations, there is a pressing need for health authorities to anticipate future CRC trends and implement age- and gender-sensitive interventions aimed at prevention, timely diagnosis, and appropriate treatment.

Acknowledgements
All authors are appreciating from the Institute for Health Metric and evaluation (IHNE) team for providing the results of the Global Burden of Disease (GBD) studies.

Compliance with ethical guidelines
This study was approved by the Research Ethics Committee of the Urmia University of Medical Sciences, Urmia, Iran (Code: IR.UMSU.REC.1402.158).

Data availability
The data supporting the findings of this study are available from the corresponding author upon reasonable request.

Funding
This research did not receive any grant from funding agencies in the public, commercial, or non-profit sectors.

Authors' contributions
Conceptualization, study design, data acquisition, review and editing: Ahmad Faramarzi and Soheila Ahmadi; Analysis and data interpretation: All authors. Writing the original draft: Ahmad Faramarzi, Soheila Ahmadi, and Naser Masoudi. 

Conflict of interest
The authors declared no conflict of interest.

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