Esophageal cancer due to dietary risk factors Deaths Trends Globally, Regionally, and Nationally, 1990-2021: An Age-Period-Cohort Analysis

doi:10.21203/rs.3.rs-4935239/v1

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Esophageal cancer due to dietary risk factors Deaths Trends Globally, Regionally, and Nationally, 1990-2021: An Age-Period-Cohort Analysis

https://doi.org/10.21203/rs.3.rs-4935239/v1

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Background

Esophageal cancer due to dietary risks (ECD) remains a global health challenge, with burden varying by dietary habits, tobacco and alcohol use. This study examines global, regional, and national ECD death trends from 1990 to 2021 using an age-period-cohort (APC) model to explore influences of aging, temporal changes, and generational shifts.

Methods

Data from the Global Burden of Disease Study 2021, encompassing 204 countries and territories, were analyzed. APC modeling was applied to assess crude and age-standardized death rates, alongside percentage changes from 1990 to 2021. Key metrics included net drift coefficients and relative death risks across age groups, periods, and cohorts.

Results

Global ECD cases decreased from 74,453.71 in 1990 to 56,939.09 in 2021, with an age-standardized death rate of 0.66 (95% CI: -0.14, 1.38) per 100,000 population. High SDI regions showed the highest overall ECD death rate (1.25, 95% CI: -0.27, 2.54 per 100,000), while low SDI regions exhibited the highest age-standardized death rate (1.48, 95% CI: -0.3, 2.88 per 100,000). India, China, USA, and Brazil reported the highest national ECD cases, with significant variations across age groups and regions.

Conclusion

A global decline in age-standardized ECD death rates is observed, especially in high-middle and middle SDI regions. Nonetheless, low SDI regions continue to experience higher rates, underscoring the need for enhanced public health interventions, including better healthcare access, early detection, and dietary modifications to reduce ECD deaths and address socioeconomic disparities.

Esophageal cancer

Age-period-cohort

Deaths

Global burden of disease study

Global health

Esophageal cancer is a significant global health concern, particularly due to its association with dietary risk factors. This malignancy often manifests through symptoms like difficulty swallowing and weight loss, which are typically indicative of advanced disease stages, resulting in poor prognoses(Daly et al., 2000). The global incidence and deaths rates of esophageal cancer have demonstrated considerable variability, influenced by regional dietary practices and genetic predispositions(“Development of Esophageal Cancer in Chaoshan Region, China,” 2015; Esophageal Cancer in the World: Incidence, Mortality and Risk Factors | Biomedical Research and Therapy, n.d.). Recent studies have identified key dietary factors such as high intake of alcohol, tobacco use, and consumption of hot beverages as major contributors to the development of esophageal cancer(“Diet and Esophageal Cancer Risk,” 2022).

The importance of understanding the trends in esophageal cancer due to dietary risk factors (ECD) deaths cannot be overstated. Such trends are critical in informing public health strategies aimed at prevention and early detection, particularly in regions with high prevalence rates. Despite the availability of comprehensive data through platforms like the Global Burden of Disease (GBD) study(Cai et al., 2022), there remains a gap in the literature concerning the detailed analysis of age, period, and cohort effects on ECD trends.

The GBD study offers a comprehensive framework for analyzing the impact of diseases and injuries across the globe(Ferrari et al., 2024). Leveraging data from GBD 2021, this study aims to provide an in-depth analysis of ECD deaths trends from 1990 to 2021, considering variations at global, regional, and national levels. An age-period-cohort (APC) model will be employed to dissect the influences of aging, temporal changes, and generational shifts on ECD deaths. This approach enables a nuanced understanding of how different cohorts and periods contribute to deaths patterns, offering insights into epidemiological transitions(Bounding Analyses of Age-Period-Cohort Effects | Demography | Duke University Press, n.d.). By visualizing ECD deaths trends by age, sex, year, and region, this study aims to elucidate the current state of ECD epidemiology, highlight geographical variations, and inform preventative measures and healthcare policies to reduce ECD incidence and deaths, mitigating its global health impact.

Data Source

This study utilized data from the Global Health Data Exchange (GHDx) GBD Results Tool (http://ghdx.healthdata.org/gbd-results-tool). The Global Burden of Disease Study 2021 (GBD 2021) evaluates the global burden of 371 diseases and injuries, including 95 communicable, maternal, neonatal, and nutritional diseases, 234 non-communicable diseases, and 40 injuries across 204 countries and territories from 1990 to 2021 (Ferrari et al., 2024). Mortality and morbidity data are derived from over 100,000 sources, including scientific literature, household surveys, epidemiological surveillance, and clinical informatics (Naghavi et al., 2024). These estimates are used to assess trends in prevalence, incidence, deaths, years lived with disability (YLDs), years of life lost (YLLs), disability-adjusted life-years (DALYs), and healthy life expectancy (HALE) (Ferrari et al., 2024, p. 202; Naghavi et al., 2024). GBD 2021 data were processed using advanced statistical models to adjust for biases and ensure consistency across different data types (“An Integrative Metaregression Framework for Descriptive Epidemiology,” n.d.; Naghavi et al., 2024; Zheng et al., 2020).

For this analysis, we extracted ECD deaths data, including all-age and age-standardized deaths rates, stratified by sex, region, age, year, and socio-demographic index (SDI) (Ferrari et al., 2024). The SDI, which combines income, education, and fertility rates, categorizes countries and regions to facilitate comparative analyses (Ferrari et al., 2024). The results are presented as the mean of 1000 simulations with 95% uncertainty intervals (UI), representing the 2.5th to 97.5th percentile range.

Statistical Analysis

Analysis of Overall Temporal Trends in Esophageal Cancer Deaths

To evaluate temporal trends in ECD deaths, we analyzed crude deaths rates across all ages, age-standardized deaths rates, and the percentage change in deaths from 1990 to 2021. Deaths rates were standardized per 100,000 person-years using global population age demographics from the GBD 2021 study (Ferrari et al., 2024). Furthermore, we examined the age-specific distribution of deaths rates by categorizing absolute deaths rates into 8 age groups (e.g., 15–49, 50–54, 55–59, ..., 75–79 years, 80 + years) and calculating the proportional representation of deaths within each age group.

Age-Period-Cohort Modeling Analysis of Deaths Data

The Age-Period-Cohort (APC) model was employed to discern deaths patterns, focusing on the effects of age, period, and cohort on ECD deaths. Key metrics include the net drift coefficient, representing the annual total percent change, and local drifts, indicating percent changes per year within age groups. Age-specific rates were adjusted for period effects to highlight age influences (Rosenberg et al., 2014). Relative deaths risks for time periods and birth cohorts were calculated to delineate period and cohort effects, respectively. Relative risks (RR) for each period were compared to a reference period, adjusting for age and non-linear cohort effects. Similarly, RR for each cohort was compared to a reference cohort, adjusting for age and non-linear period influences. An RR greater than 1 suggests an increased deaths risk, while an RR less than 1 indicates a decreased risk.

To address collinearity issues among age, period, and cohort variables, we utilized the intrinsic estimator approach within the APC framework. This method overcomes the indeterminate nature of model parameters (Y. Yang et al., 2008). The APC model incorporated ECD deaths estimates from GBD 2021, utilizing uniform age and period intervals, including 14 age categories (25–29, 30–34, 35–39, ..., 85–89 years, 90 + years) and 19 partially overlapping ten-year birth cohorts spanning from 1901–1909 (1905 cohort) to 1991–1999 (1995 cohort). Statistical analyses were conducted using two-tailed tests with a significance level set at p < 0.05. APC analysis was facilitated by the web-based application for APC modeling from the National Cancer Institute (http://analysistools.nci.nih.gov/apc/)(Bell, 2020; Rosenberg & Anderson, 2011), and all visualizations were generated using R statistical software (version 4.0.3).

Trends of deaths rate of ECD, 1990–2021

Table 1, Fig. 1A, Fig. 1B, Fig. 2, and Supplementary Table 1 provide data on population, total deaths, all-age deaths rate, age-standardized deaths rate, and net drift of the deaths rate. Between 1990 and 2021, the global number of ECD cases decreased from 74453.71 (95% CI (Confidence interval): -16380.28, 147090.67) to 56939.09 (95% CI: -12023.44, 118369.96), with an age-standardized deaths rate of 0.66 (95% CI: -0.14, 1.38) per 100,000 population. The global APC model predicted a net drift of -3.86 (95% CI: -3.96, -3.75) in ECD deaths during this period.

Regionally, high SDI areas exhibited the highest overall ECD deaths rate at 1.25 (95% CI: -0.27, 2.54) per 100,000 population compared to high-middle SDI regions at 0.51 (95% CI: -0.1, 1.19) per 100,000 population in 2021. Conversely, regions with low SDI had the highest age-standardized deaths rate of ECD at 1.48 (95% CI: -0.3, 2.88) per 100,000 population, while regions with high-middle SDI had the lowest deaths rate of 0.34 (95% CI: -0.07, 0.79) per 100,000 population. The net drift outcomes predicted by the APC model showed the opposite trends.

At the national level, countries with the highest ECD cases included India (8484.66, 95% CI: -1885.9, 17051.27), China (8400.67, 95% CI: -1624.28, 24326.31), USA (3931.87, 95% CI: -856.59, 7915.84), and Brazil (2913.83, 95% CI: -664.2, 5786.9). In 2021, UK had the highest overall ECD deaths rate (2.95, 95% CI: -0.64, 5.84 per 100,000), while Egypt had the lowest (0, 95% CI: 0, 0.01 per 100,000). Malawi exhibited the highest age-standardized ECD deaths (7.14, 95% CI: -1.49, 14.24 per 100,000 population), while Egypt had the lowest (0.01, 95% CI: 0, 0.04 per 100,000 population). Furthermore, net drifts ranged from 14.76 (95% CI: 2.69, 28.25) in Greece to -19.13 (95% CI: -51.4, 34.57) in Armenia (Fig. 2, Supplementary Table 1).

Temporal trends in the Deaths of ECD across age groups

Figure 3A shows global downward drift in ECD deaths across all ages from 1990–2021, with the greatest annual reduction of -4.417% per year (95% CI -4.571 to -4.263) in the 45–49 years age group. After 45–49 years of age, the decline diminishes with age to -0.812% (95% CI -1.260 to -0.363) at 85–89 years of age. Similar patterns occurred high, high-middle, and middle-SDI regions. The 35–39 years age group in high-middle SDI countries had the largest decline at -8.825% per year (95% CI -9.602 to -8.042). low-middle and low SDI countries showed smaller declines, with an upward trend of 0.114% (95% CI -1.300 to 1.548) in low SDI among 85–89 years. Before 50 years, deaths declined more in men, while after 50 years, declines were greater in women. The decline was generally smaller for men than for women in the low and low-middle SDI, but there was little difference between both genders in low SDI after 65 years.

Figure 3B shows temporal changes in the age distribution of ECD deaths. In 1990, over 75% of global ECD cases were in middle-aged and older adults ≥ 50 years, with 65–69 years old accounting for the largest proportion. Between 1990 and 2021, the number of ECD deaths in the 80 + age group increases significantly globally, finally accounting for the largest proportion. A similar pattern occurred across all regions except low and low-middle SDI. Among regions, cases in 80 + age elderly rose most significantly in high, high-middle, and middle SDI areas, while cases remained almost stable across age groups in low and low-middle SDI regions. Supplementary Fig. 2 depicts the age distributions of deaths by country.

Effects of age, period, and cohort on the deaths rate of ECD

Figure 4 delineates the appraisals of age, period, and cohort effects stratified by SDI quintile. On the whole, comparable age effect trends were observed across all SDI quintiles except for high SDI areas. The deaths of ECD escalate with advancing age, reaching its apex in the 80–84 years age groups, and then decreases in the 85–89 years age groups, but peaks in the 85–89 years age groups in areas of high SDI. (Fig. 4A). Global gender differences were found in age effects, with deaths rates for males considerably higher than those for females, but in the low SDI region, females had a higher deaths rate than males in the age group after 80 years of age.

Globally, the period effect shows a gradual decrease in ECD deaths risk over time (Fig. 4B). Similar declining period trends occurred across all regions, with the largest decreases in high-middle and middle SDI. Period effects differed little by sex except in the low-middle and low SDI regions where females had higher contemporaneous deaths than males prior to 2003 and males had higher contemporaneous deaths than females after 2003, suggesting differences between higher and lower SDI regions.

Globally, the risk of ECD death decreases progressively in younger birth cohorts, peaking in the 1920 cohort, with consistent trends across high, low-middle, and low SDI regions. The trends in high-middle and middle SDI regions align closely with the global trend, with the 1920 cohort exhibiting a higher risk of death than previous cohorts, but not the highest. Post-1920 cohorts show a gradual decline in death risk with younger age groups (Fig. 4C). In pre-1950 cohorts, females had a significantly higher risk of death than males. However, post-1950, the risk difference between genders diminished, except in low-middle and low SDI regions, where males had a higher risk. There was no significant gender difference in low SDI regions before 1950. Supplementary Figs. 3–5 detail ECD deaths by age, period, and birth cohorts for each country.

Age, Period, and Cohort effects on Deaths Patterns in Selected Country

In order to better elucidate the prominent variations in the deaths rate of ECD across age, period, and cohort effects worldwide, we presented multiple exemplar nations from diverse SDI quintiles. Figure 5A depicts nations with advantageous APC effects, suggesting decreased ECD deaths risk. Qatar is typically a high SDI country. In Qatar, ECD deaths rates have declined sharply each year in all age groups, with a general downward trend in period effects and a reduction in risk as birth cohorts become younger. Kazakhstan, which is representative of the high-middle region of the SDI, has experienced significant annual declines in ECD deaths rates in all age groups, with the largest declines occurring in the age group around 55 years of age, a gradual decrease in the deaths rate with the period effect and the youth of the birth cohort, and a significant difference in the deaths rates of men and women in the age group after 40 years of age. Uzbekistan belongs to the middle SDI countries, with significant annual declines in ECD deaths rates at all ages, and period and cohort risk reductions. Among countries with low-middle SDI, Kyrgyzstan has the largest annual decline in ECD deaths rate at all ages, with decreasing period and cohort risk. Rwanda had the largest decline in ECD deaths rate among low SDI countries in all age groups, but the decline diminished with age, with both period and cohort effects trending downward.

The data presented in Fig. 5B depicts nations exhibiting relatively disadvantageous APC effects on deaths rates, suggesting an elevated risk for ECD onset within those populations. In the United Arab Emirates, the ECD deaths rate for all age groups has increased substantially each year, with cohort risk increasing with younger birth cohorts, and the period effect has been increasing overall, but declining slightly after 2010. Among the high-middle SDI areas, the greatest increases in annual ECD deaths rates were observed in all age groups in Greece, particularly in the pre-55 age group, while period effects and birth cohort risk effects were both increasing. Fiji is a middle SDI country with an increasing trend in annual ECD deaths rate in all age groups. Period effect significantly increased the risk in 2005, with a higher risk of period effect in females than in males, and cohort risk increasing with the younger birth cohort. In the low-middle SDI region, the annual deaths rate of ECD in all age groups in Mauritania show a local drift of more than 0% per year, accompanied by a significant cohort risk effect and a significantly higher period risk. In the low SDI region, Sierra Leone experienced significant annual ECD deaths rate increases in all age groups, with increasing ECD deaths and worsening cohort risk over time.

This study examined global, regional, and national trends in ECD deaths from 1990 to 2021 using the GBD 2021 data and an APC model. The analysis highlighted significant reductions in ECD deaths rates globally, with pronounced variations across different regions and countries. Middle-aged and older adults bear a disproportionate burden of ECD. Understanding these temporal and geographical patterns is essential for identifying contributing factors and directing targeted prevention and treatment strategies to mitigate the global burden of ECD.

Globally, the age-standardized death rate of ECD declined from 1990 to 2021, with the global number of cases decreasing from 74,453.71 to 56,939.09. In 2021, High SDI regions exhibited the highest ECD death rates, while low SDI regions had the highest age-standardized death rates. Negative net drift is significantly smaller in high, high-middle, and middle SDI regions than in low-middle and low SDI regions, suggesting that the burden of ECD deaths decreases with socioeconomic development, consistent with previous studies showing an overall decrease in ECD DALYs since 1990(Jiang et al., 2023). Nationally, India, China, the USA, and Brazil reported the highest ECD cases. The UK had the highest death rate in 2021, while Egypt had the lowest. Malawi had the highest age-standardized death rate, and Armenia showed the largest negative net drift.

The decline in ECD deaths rates can be attributed to several factors, including advancements in medical technologies, improved early detection, and effective treatment protocols(Whooley et al., 2001). Public health initiatives aimed at reducing known risk factors, such as tobacco and alcohol consumption, and poor dietary habits, have played a crucial role in lowering ECD incidence and deaths rates(Castellsagué et al., 2000; Ishikawa et al., 2006). Dietary factors, in particular, have a significant impact on ECD risk. Studies indicate that diets high in processed foods and red meat, and low in fruits and vegetables, increase the risk of ECD(Bravi et al., 2012; “Diet and Esophageal Cancer Risk,” 2022). Researchers demonstrated a strong association between poor dietary habits and esophageal squamous cell carcinoma, especially in low- and middle-income countries(Chetwood et al., 2019). E. Riboli et al. (2003) highlighted the protective effects of diets rich in fruits and vegetables against ECD(“Epidemiologic Evidence of the Protective Effect of Fruit and Vegetables on Cancer Risk,” 2003).

In countries like Kazakhstan and Rwanda, significant reductions in ECD deaths rate were observed. In Kazakhstan, the sharp decline in deaths rate across all age groups can be linked to enhanced healthcare infrastructure, widespread screening programs, and effective public health policies targeting key risk factors, including dietary improvements(Igissinov et al., 2012). For Rwanda, the improvements in healthcare access and socioeconomic conditions have likely played a critical role in the observed deaths rate reduction(Fadelu et al., 2022; Shulman et al., 2014; Stulac et al., 2015). Dietary modifications, including increased consumption of fruits and vegetables and reduced intake of processed foods, have also contributed to these positive trends(Liu et al., 2017).

In populous countries such as India, China, and the USA, the trends are diverse. India's decrease in ECD deaths rate is associated with nationwide anti-tobacco campaigns, alcohol reduction initiatives, and improved nutritional practices(Samarasam, 2017). Despite these efforts, regional disparities persist, particularly in rural areas with limited healthcare access and lower socioeconomic status(Kapoor et al., 2015). China's significant decline in ECD deaths rate reflects successful public health campaigns targeting smoking cessation and alcohol moderation, alongside dietary improvements(Gao et al., 2017; C. S. Yang & Chen, 2021). However, high incidence rates in certain provinces highlight the need for ongoing efforts(“Esophageal Cancer in High-Risk Areas of China,” 2017; Sun et al., 2017). In the USA, the modest decline in ECD deaths rate can be attributed to population aging and advancements in medical care and public health policies(Xia et al., 2022). Socioeconomic disparities affecting access to healthcare result in varied deaths rates across states and demographic groups(Schlottmann et al., 2020). Another study showed that the reduction in ECD death rates in America is influenced by a decreased incidence among black individuals and an increased incidence of adenocarcinoma in the Midwest and Northeast(Patel et al., 2018).

This study has limitations. First, ECD deaths data accuracy from administrative records may be limited, especially in developing regions with less robust surveillance. Second, only epidemiological trends were examined, not severity, quality of life, survival, or costs. Future research should obtain more precise, standardized ECD deaths through large multi-national cohort studies with systematic screening and diagnosis confirmation. Assessing severity with validated scales, analyzing DALYs, incidence, and costs could provide comprehensive information on global ECD burden and impacts.

In conclusion, this study provides updated global and regional ECD deaths estimates from 1990 to 2021 using APC modeling. The findings reveal significant declines in age-standardized ECD deaths rates, particularly in high-middle and middle SDI regions. However, low SDI regions continue to experience higher age-standardized ECD deaths rates in 2021, emphasizing the need for targeted public health interventions. Continued efforts to reduce ECD deaths should focus on improving healthcare access, enhancing early detection, and addressing socioeconomic disparities. Dietary improvements, particularly increased consumption of fruits and vegetables and reduced intake of processed foods, are essential components of these efforts. Regular surveillance and standardized data collection are critical for monitoring ECD incidence and informing effective control strategies.

Disclosure of interest

The authors report there are no competing interests to declare.

Ethics approval and consent to participate

The data utilized in this study were anonymized prior to analysis, thus exempting the work from ethical approval procedures. The methodology employed adhered to pertinent protocols and regulatory standards.

Funding

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

Author Contribution

YYZ, YJ, and WHL formulated the study concept. YYZ, YJ retrieved and compiled the raw data, executed initial analyses, generated tables and figures, and produced the preliminary manuscript draft. YYZ, BZX, and HYC assisted with data interpretation. YYZ, WHL, RRS, and YDH critically evaluated the results. YYZ, YJ, WHL and HYC significantly revised and critically evaluated the manuscript. YYZ oversaw all deaths modeling data. YYZ directed the overall research program. YYZ, YJ and RRS provided general oversight and made the final decision regarding submission for publication. After reviewing the article draft, all authors read the finalized manuscript and granted approval for submission for publication.

Acknowledgement

We would like to express thanks to the Global Burden of Disease study for making this research possible through the provision of publicly available data.

Data Availability

All data used in this study can be freely accessed at the Global Burden of Disease 2021 portal (https://vizhub.healthdata.org/gbd-results/).

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Table 1 is available in the Supplementary Files section.

No competing interests reported.

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Esophageal cancer due to dietary risk factors Deaths Trends Globally, Regionally, and Nationally, 1990-2021: An Age-Period-Cohort Analysis

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Version 1

Abstract

Background

Methods

Results

Conclusion

Figures

Introduction

Materials and Methods

Data Source

Statistical Analysis

Analysis of Overall Temporal Trends in Esophageal Cancer Deaths

Age-Period-Cohort Modeling Analysis of Deaths Data

Results

Trends of deaths rate of ECD, 1990–2021

Temporal trends in the Deaths of ECD across age groups

Effects of age, period, and cohort on the deaths rate of ECD

Age, Period, and Cohort effects on Deaths Patterns in Selected Country

Discussion

Declarations

Disclosure of interest

Funding

Author Contribution

Acknowledgement

Data Availability

References

Tables

Additional Declarations

Supplementary Files

Status:

Version 1