The burden of Gastric Cancer and possible risk factors from 1990 to 2021，and projections until 2035: findings from the Global Burden of Disease Study 2021

doi:10.21203/rs.3.rs-5296633/v1

Background

Gastric cancer exhibit high morbidity and mortality rate in China, resulting in substantial disease burdens. A comprehensive evaluation of the burden is crucial to improve strategies for gastric cancer prevention and treatment.

Methods

We collected incidence, deaths, disability-adjusted life-years (DALYs), age-standardized incidence rate(ASIR), age-standardized death rate (ASDR), age-standardized DALY rate (ASR) of gastric cancer at the global, regional, and national levels in all 204 countries and territories from 21 regions during 1990 to 2021. The Bayesian age-period-cohort model was applied to project future trends until 2035.

Results

In 2021, The new cases, deaths and DALYs of gastric cancer increased. More than 1.23 million incident cases of gastric cancer were reported worldwide, which caused 954373.60 deaths and 22786633.10 DAYLs. The age-standardized rates for incidence, death and DALYs decreased by-42%(-49% to -35%),-49%(-55% to -43%) and − 53%(-58% to -47%) from 1990 to 2021, respectively. The highest age-standardized incidence and death rates in 2021 were observed in the High-middle SDI quintile. Both the age-standardized death, incidence and DALYs rate among males were all higher than those among females. In 2021, East Asia and High-income North America had the highest disease burden related to smoking, and Central Europe had the highest disease burden related to diet high in sodium. Furthermore, projections suggest that the ASIR and ASDR of gastric cancer will likely follow steady downward trends by 2035.

Conclusions

Gastric cancer continued to cause a heavy burden globally and in different countries and regions, with significant decreased in the incidence and mortality. Death and DALY rates attributable to high sodium diet and smoking have generally declined. There are still significant differences between age groups and regions. Targeted preventive measures, such as controlling smoking and increasing intake of fresh vegetables and fruits, should be taken in the future to reduce the risk of gastric cancer

Global Burden of Disease

Gastric cancer

Risk factors

Death

Disability-Adjusted Life Years

Gastric cancer is the one of the most commonly cancers worldwide(1), According to estimates from the International Agency for Research on Cancer (IARC) GLOBOCAN project, gastric cancer was the fifth most commonly diagnosed type of cancer in 2018, accounting for 8.2% of all cancer deaths(2). As a malignant tumor, gastric cancer posed a significant disease burden(3).Despite declines in gastric cancer incidence and mortality over the past few decades, there will still be 1.089 million new cancer cases and 0.769 million deaths worldwide in 2020(4). The incidence and mortality rates of gastric cancer large vary widely around the world. In recent decades, gastric cancer incidence and mortality have steadily declined in developed countries(5). In recent years, historically high levels of gastric cancer cases and deaths have been seen in East Asia, where there are large populations, but a downward trend has also been observed. In 2018, among all populations, gastric cancer death rates were highest in East Asia (15.9 per 100,000 people) and lowest in North America (1.8 per 100,000 people)(6).

Proper preventive measures should be taken because prevention is an important way to control this cancer and reduce its mortality rate(7). Prevention depends on accurate identification of risk factors for gastric cancer(8). Studies have confirmed that gastric cancer is a multifactorial disease, and the risk factors include Helicobacter pylori infection, environmental and genetic factors, and lifestyles(9). Lifestyle factors, such as a high-sodium diet and smoking, can have a significant and profound impact on cancer over a lifetime(10, 11). A Meta-Analysis of Case-Control Studies showed a significantly positive association between high salt intake and gastric cancer compared with low salt intake(OR = 1.55, 95% CI (1.45, 1.64); p < 0.001). Higher dietary salt intake increased the risk of gastric cancer(12).

The burden of gastric cancer in different regions may be significantly affected by many factors such as geographical location, dietary habits and medical level. Studies have shown that East Asian countries (such as China, Japan, and South Korea) have significantly higher rates of gastric cancer incidence and death than Western countries, including the United States(13). East Asian countries account for two-thirds of stomach cancer cases worldwide, largely due to the prevalence of Helicobacter pylori (Hp) infection and related dietary habits, among other factors(14). Therefore, comparing the disease burden, risk factors and time trends of gastric cancer in different countries and regions not only helps decision makers to have an in-depth understanding of the global epidemic trend of gastric cancer, but also provides an important reference for formulating more accurate and effective prevention and control strategies.

While previous studies have reported estimates of stomach cancer disease burden, they have been limited to regions or countries with limited analysis, such as those in East Asia. Recent data on the burden and trends in gastric cancer incidence and mortality are still poorly understood. The latest study analyzed the global burden of stomach cancer disease in adolescents and young adults, and did not systematically analyze the burden of stomach cancer disease in the overall population globally and in different regions.

This study aimed to compare the burden, trends, and possible risk factors of gastric cancer in different countries and regions from 1990 to 2021 based on the Global Burden of Disease (GBD) Study 2021.Furthermore, we projected the cancer burden until 2030. Understanding the latest burden patterns will help policymakers o better allocate health resources and reduce gastric cancer burden.

Data sources

The data of gastric cancer data for the 1990–2021 period came from the Global Health

Data Exchange (GHDx) query tool. In this study, we acquired data on the number of deaths, incidence and DALYs, age-standardized death rate(ASDR), age-standardized incidence rate(ASIR), age-standardized DALYs rate(ASR) and possible risk factors of gastric cancer from the GBD 2021. Previous studies have described GBD research methods. Socio-demographic index (SDI) is an aggregative indicator that is calculated by integrating with the lag-distributed income per capita, with educated experience for those age > 15 and above to reflect the economic status of certain geographical locations(15). SDI varies between 0 and 1, with higher SDI implying better socioeconomic development. Based on the SDI, regions are classified into five classes, including low (< 0.46), low-middle (0.46–0.60), middle (0.61–0.69), high-middle (0.70–0.81) and high SDI (> 0.81)(16). In addition, we predict the ASDR and ASIR of gastric cancer in the different age groups from 2022 to 2032.

Statistical analysis

To avoid the disparity of the age distribution of the populations, the ASDR, ASIR and ASR was used to quantify the burden and trends of gastric cancer in different regions based on the GBD Standard Population Distribution(17). The Bayesian age-period-cohort (BAPC) model has been proven to have higher accuracy in predicting the cancer burden, compared with the generalized additive model, Joinpoint model and Poisson regression(18).In our study, the BAPC model with integrated nested Laplace approximation was used to predict the ASIR and ASDR trends of gastric cancer from 2022 to 2032.

Burden of gastric cancer in 2021

The number of gastric cancer deaths cases worldwide in 2021 was 954373.60, and the number of gastric cancer incidence cases was more than 1.23 million. The age-standardized death rate of gastric cancer was 11.2 per 100000 person-year, with a -49% (-55% to -43%) decrease since 1990. The age-standardized incidence rate of 14.33 per 100000 person-year, with a -42% (-49% to -35%) decrease since 1990. Gastric cancer contributed to 22786633.10 DAYLs worldwide in 2021.The age-standardized DALYs rate was 262.75, which had declined by − 53% (-58% to-47%) from 1990 to 2021 (Table 1).

Table 1. Incidence, deaths and DALYs of gastric cancer in 2021, and percentage change of age-standardized rates by GBD region

World region	Deaths				Incidence			DALYs
World region	Number of death cases	ASDR per 100 000		Percentage change in rates, between 1990 and 2021	Number of incidence cases	ASIR per 100000	Percentage change in rates, between 1990 and 2021	Number of DALYs	ASR per 100 000	Percentage change in rates, between 1990 and 2021
global	954373.60		11.20	-0.49(-0.55 to -0.43)	1230232.61	14.33	-0.42(-0.49 to -0.35)	22786633.10	262.75	-0.53(-0.58 to -0.47)
Low SDI	41191.89		8.46	-0.29(-0.36 to -0.19)	41388.33	8.13	-0.29(-0.36 to -0.19)	1198903.09	209.77	-0.33(-0.40 to -0.23)
Low-middle SDI	107456.07		7.71	-0.26(-0.34 to -0.17)	110396.16	7.68	-0.24(-0.32 to -0.14)	2953125.30	192.56	-0.30(-0.37 to -0.21)
Middle SDI	356459.41		13.72	-0.51(-0.59 to -0.42)	451464.69	16.91	-0.41(-0.51 to -0.29)	8820717.05	320.24	-0.56(-0.63 to -0.46)
High-middle SDI	295104.98		14.93	-0.52(-0.59 to -0.44)	387196.45	19.62	-0.41(-0.50 to -0.30)	6901607.26	353.18	-0.56(-0.63--0.47)
High SDI	153539.22		6.83	-0.57(-0.59 to -0.55)	239119.14	11.16	-0.52(-0.54 to -0.49)	2897404.07	146.10	-0.62(-0.64 to -0.59)
Andean Latin America	12367.85		21.33	-0.35(-0.47 to -0.19)	12592.61	21.48	-0.31(-0.44 to -0.13)	292674.83	485.41	-0.37(-0.50 to -0.21)
Australasia	2190.60		3.91	-0.49(-0.54 to -0.45)	3187.03	5.93	-0.42(-0.47 to -0.37)	42611.53	84.88	-0.51(-0.55 to -0.46)
Caribbean	4190.77		7.79	-0.37(-0.45 to -0.28)	4278.60	7.97	-0.34(-0.43 to -0.25)	104401.71	195.67	-0.34(-0.44 to -0.23)
Central Asia	9331.81		11.56	-0.56(-0.60 to -0.51)	9763.16	11.78	-0.55(-0.60 to -0.51)	264444.68	298.62	-0.59(-0.63 to -0.54)
Central Europe	19181.72		8.54	-0.54(-0.57 to -0.50)	20268.79	9.19	-0.50(-0.54 to -0.46)	418847.72	201.30	-0.55(-0.58 to -0.51)
Central Latin America	28762.54		11.69	-0.45(-0.50 to -0.38)	29823.80	11.98	-0.41(-0.47 to -0.34)	722802.90	282.56	-0.41(-0.48 to -0.34)
Central Sub-Saharan Africa	4606.57		8.93	-0.26(-0.42 to -0.05)	4664.05	8.54	-0.26(-0.42 to -0.05)	139267.22	220.04	-0.28(-0.45 to -0.06)
East Asia	455946.78		21.26	-0.53(-0.62 to -0.40)	624688.18	28.64	-0.39(-0.52 to -0.21)	10921588.63	496.94	-0.57(-0.66 to -0.44)
Eastern Europe	42700.45		12.15	-0.59(-0.62 to -0.56)	51005.67	14.67	-0.55(-0.59 to -0.52)	1031464.99	306.55	-0.62(-0.65 to -0.59)
Eastern Sub-Saharan Africa	11541.76		7.09	-0.36(-0.44 to -0.25)	11642.22	6.80	-0.36(-0.44 to -0.25)	344563.81	175.48	-0.40(-0.48 to -0.29)
High-income Asia Pacific	70689.30		13.13	-0.65(-0.67 to -0.62)	123451.50	25.43	-0.61(-0.64 to -0.58)	1194020.53	273.07	-0.70(-0.72 to -0.67)
High-income North America	19363.35		2.95	-0.47(-0.49 to -0.45)	33112.80	5.23	-0.37(-0.39 to -0.35)	419797.65	70.88	-0.45(-0.47 to -0.44)
North Africa and Middle East	39717.13		9.43	-0.38(-0.45 to -0.29)	42569.24	9.67	-0.34(-0.42 to -0.25)	1057331.88	217.41	-0.43(-0.50 to -0.35)
Oceania	956.95		13.45	-0.24(-0.40 to -0.04)	1008.81	13.26	-0.23(-0.39 to -0.02)	30296.40	341.81	-0.25(-0.43 to -0.03)
South Asia	82924.31		5.72	-0.27(-0.37 to -0.15)	84803.45	5.70	-0.26(-0.36 to -0.13)	2295874.98	145.55	-0.32(-0.41 to -0.21)
Southeast Asia	43302.95		6.83	-0.37(-0.45 to -0.24)	47761.06	7.27	-0.32(-0.41 to -0.18)	1193413.33	170.78	-0.40(-0.48 to -0.27)
Southern Latin America	9292.35		10.51	-0.44(-0.49 to -0.38)	9965.29	11.39	-0.39(-0.44 to -0.33)	205763.26	241.14	-0.44(-0.49 to -0.39)
Southern Sub-Saharan Africa	3967.35		7.13	-0.12(-0.22 to -0.01)	4054.55	7.02	-0.11(-0.21 to -0.00)	111785.25	177.66	-0.15(-0.25 to -0.03)
Tropical Latin America	24866.82		9.78	-0.50(-0.52 to -0.48)	25610.57	9.99	-0.47(-0.50 to -0.45)	619369.49	237.81	-0.49(-0.51 to -0.46)
Western Europe	56321.73		5.57	-0.62(-0.64 to -0.60)	73910.78	7.81	-0.54(-0.56 to -0.52)	1038056.54	120.38	-0.62(-0.64 to -0.60)
Western Sub-Saharan Africa	12150.50		6.69	-0.16(-0.30 to -0.02)	12070.47	6.33	-0.16(-0.31 to -0.02)	338255.78	156.08	-0.21(-0.35 to -0.06)

ASDR, the age-standardized death rate. ASIR, the age-standardized incidence rate. ASR, the age-standardized DALYs rate.

In 2021, the highest age-standardized death rates of gastric cancer were observed in the High-middle SDI quintile (14.93 per 100,000 person-years), whereas the lowest rate was observed in the high SDI quintile (6.83). The highest age-standardized incidence rates of gastric cancer were in the High-middle SDI quintile (19.62), and the lowest rate was observed in the Low-middle SDI quintile (7.68).

Regionally, the ASDR per 100000 person-year in 2021 was highest in Andean Latin America(21.33),followed by East Asia(21.26),and the lowest in High-income North America(2.95). The top 5 regions for ASIR per 100000 person-year were East Asia(28.64), high-income Asia Pacific(25.43), Andean Latin America(21.48), Eastern Europe(14.67), Oceania(13.26). We observed large differences in the age-standardized DALYs rates across regions. The age-standardized DALYs rates per 100000 person-year in 2021 was highest in East Asia(496.94),followed by Andean Latin America(485.41),Oceania(341.81).The lowest were in Australasia(84.88) and High-income North America(70.88).

The 2021 global map of the age-standardized death, incidence and DALYs rates of gastric cancer is presented in Figure1. The countries with the highest ASDR in gastric cancer occur mainly in Peru, Bolivia, and Ecuador in Andean Latin America and China and Mongolia in East Asia. The lowest were in the United States, Canada, Australia, Algeria and Saudi Arabia(Figure 1A). One of the countries with the lowest ASIR was the United States. In East Asia, China, Mongolia, Japan and South Korea were the countries with the highest age-standardized incidence rate(Figure1B). Both the age-standardized death, incidence and DALYs rate among males were all higher than those among females in 2021(Figure 2).

Time Trends of gastric cancer disease burden in regions with different SDI levels from 1990 to 2021

The ASDR, ASIR and ASR of gastric cancer decreased worldwide from 1990 to 2021(Table1, Figure 2). During this period, the age-standardized incidence, death and DALYs rates were decreased in both males and females, with a more pronounced downward trend in males. There were obvious decreases in the ASDR, ASIR and ASR between 1990 and 2021 in all SDI regions. The greatest decrease in ASDR, ASIR and ASR was in the high-middle SDI regions, followed by middle SDI regions, high SDI regions (Figure 2). The ASDR in high SDI, low-middle SDI and low SDI regions were lower the global level (Figure 2A).The ASIR in high-middle SDI and middle SDI regions were higher than the global level from 1990 to 2021(Figure 2B).The age- standardized DALYs rate in high-middle SDI and middle SDI regions were higher than the global level, while the age-standardized DALYs rates in the high SDI ,low-middle SDI and low SDI regions were lower than the global level(Figure 2C).

Gastric cancer incidence and death in relation to SDI

Figure 3 illustrates the secular trend in age-standardized death, incidence and DALYs rates of gastric cancer across the SDI quintiles by regions from 1990 to 2021 and the expected levels based only on the SDI values of the global regions. There were obvious differences in the effects of SDI among the different regions. We found that an overall downward trend in most regions. The expected age-standardized incidence, death and DALYs rates decreased with increasing SDI values. The age-standardized death rate in High−income Asia Pacific and Central Asia decreased sharply with increasing SDI value(Figure 3A).

The age-standardized incidence rate in High−income Asia Pacific and Eastern Europe decreased sharply whereas South Asia and Western Sub−Saharan Africa decreased slowly with increasing SDI value. The age-standardized incidence rate in East Asia initially decreased, then slowly increased, peaked at an SDI of 0.6 and then decreased remarkably with increasing SDI value(Figure 3B). The correlation of the SDI with age-standardized DALYs rate was similar to that with the age-standardized death rate(Figure 3C).

Risk factors for gastric cancer

The proportion of age-standardized death and DALYs for gastric cancer being attributed to smoking peaked in the 70-74 age group, and attributed to high-sodium diets peaked in the 55-59 and 65-69 age groups in 2021(Figure 4).

The trends of age-standardized death and DALYs attributable to a high-sodium diet and smoking from 1990 to 2021 varied among the worldwide and global regions. Globally, 7.93% of age-standardized death were attributed to high-sodium diets, 11.18% of the age-standardized death were attributable to smoking. 7.92% of age-standardized DALYs were attributed to high-sodium diets, 11.02% of the age-standardized DALYs were attributable to smoking (Figure 5). We observed that middle SDI, high-middle SDI and high SDI were more affected by smoking, while low SDI, low-middle SDI were more affected by high-sodium diets. Smoking accounts for a small proportion of age-standardized DALY globally, but in East Asia and high-income North America, smoking contributes more than 12% to age-standardized DALY for gastric cancer.

In 2021, the proportion of age-standardized death attributable to smoking was highest in East Asia, followed by High-income North America, and the lowest in Western Sub-Saharan Africa(Figure 5A). The proportion of age-standardized death attributable to diet high in sodium was highest in Central Europe. The proportion of age-standardized DALYs attributable to diet high in sodium was highest in Central Europe, and the lowest in North Africa and Middle East(Figure 5B).

Predictions of gastric cancer from 2022 to 2032

Utilising Bayesian age-period-cohort (BAPC) models, we predict the ASIR and ASDR of gastric cancer in different age from 2022 to 2035. We found that the ASDR and the ASIR of gastric cancer will experience a continuous decline(Figure 6).We forecast that the ASDR of gastric cancer in the different age groups will live off or continuous decline over this timeframe, consistent with the downward trend observed from 1990 to 2021. The ASDR of gastric cancer in 45-49,50-54 and 70-74 age groups are expected to display stable and leveling trends during this period, which is markedly different from the large declines observed from 1990 to 2021. We observed that the ASDR for gastric cancer in the 90-94 age group and 95 + age group did not decline significantly from 1990 to 2021, however, we predicted that gastric cancer in these two age groups would decline significantly over this time frame((Additional file).Additionally, we predict that the ASIR of gastric cancer in 70-74 age group and 75-79 age group will significantly decrease, consistent with the downward trend observed from 1990 to 2021((Additional file).

Gastric cancer is becoming a global health challenge with high morbidity and mortality, requiring increased attention and efforts to reduce its severe damage(19). This study revealed the most updated temporal and geographical trends of gastric cancer burden at the global, regional, and national levels from 1990 to 2021 based on the GBD 2021 study. Between 1990 and 2021, we found although the absolute number of gastric cancer cases, DALYs, and deaths increased, the age-standardized rates for incidence, DALYs, and deaths dropped, during this period. Globally, the age-standardized death rate for gastric cancer in 2021 was 11.2 per 100,000 person-years, and the age-standardized incidence rate was 14.33 per 100,000 person-years, both lower than in 2019 (ASDR, 12 per 100,000 person-years and ASIR, 16 per 100,000 person-years)[3]. Although the age-standardized incidence and death of gastric cancer are declining globally, the aging population and changes in lifestyle and population growth may lead to a " morbidity and mortality decline, but the number of cases and deaths increase " of gastric cancer(20).

The burden of gastric cancer continues to vary geographically across regions of the world, but incidence rate continues to decline in most countries and are predicted to follow this trend into the future(21). We observed that the high SDI quintile had the lowest age-standardized death rate for gastric cancer, and had a lower age- standardized incidence rate of gastric cancer. The largest decrease in age-standardized incidence rate for gastric cancer was mainly attributable to lifestyle and hygiene changes such as a reduced consumption of foods preserved by salting or smoking, and a reduction in the prevalence of Helicobacter pylori (H. pylori) infection(22, 23).The low SDI quintile had a lower burden of gastric cancer, and both mortality and morbidity were lower. One plausible explanation is that cancer incidence and mortality are often underreported due to potential misdiagnoses and missed diagnoses, poorly developed infrastructure, and weak cancer surveillance systems when resources are unevenly distributed(24).

This study found that the highest incidence of gastric cancer in East Asia, which is consistent with findings from previous studies(25). The region with the highest mortality rate of gastric cancer was Andean Latin America, and East Asia has fallen to second place. Although the mortality rate in East Asia was not the highest, our results estimate that East Asia accounts for 47.78% of the global deaths and more than 50% of the global incidence cases of gastric cancer of cancer deaths. This show that the disease burden of gastric cancer in East Asia still remains serious, with morbidity and mortality rates still higher than the world average. High-income North America and Australasia reported the lowest age-standardized death rates, consistent with previous findings(26).

As prevention, screening, and treatment programs have been implemented worldwide, gastric cancer incidence and mortality rates have steadily declined in most countries over the past few decades(27, 28).

At the country level, the highest age-standardized rates for incidence and death of gastric cancer were noted in Mongolia, Afghanistan and Bolivia. China and Republic of Korea had the next highest age-standardized incidence rates. The five countries with the highest age-standardized incidence rates in Asia were Mongolia(36.83), Afghanistan(32.93), China(29.05), Republic of Korea(25.76) and Japan(25.54).This result is inconsistent with previous research. The GLOBOCAN 2020 database (https://gco.iarc.fr/) estimated that the five countries reported to have the highest ASIR in Asia are Mongolia (32.5), Japan (31.6), South Korea (27.9), Tajikistan (23.4) and China (20.6)(4, 29). Although the ASIR of gastric cancer continues to decrease in most countries, the incidence of gastric cancer was on the rise in Mongolia and China. Mongolia has the highest incidence and mortality rates, mainly due to the lack of endoscopy and professional endoscopists(30).Because the early symptoms of gastric cancer are occult, most patients with gastric cancer are at an advanced stage of metastasis at diagnosis(31).Due to the lack of awareness of early screening, the detection rate of early cancer is low, which affects the prognosis and burden of cancer patients(32). A steady decline in incidence for gastric cancer has been observed in China over the past several decades. With the popularity of gastrointestinal endoscopy, China has proposed a series of guidelines aimed at improving gastric cancer screening, early detection and treatment strategies, and the proportion of early gastric cancer in China has increased in recent years, and most cases are detected through early screening(33). It is worth noting that the disease burden of stomach cancer in Japan has decreased significantly. The death rate of gastric cancer was low in Western countries such as the United States. The 5-year overall survival (OS) shows gastric cancer survival as a result of advances in diagnostic and treatment strategies, especially early detection using endoscopic and/or radiological methods from national screening programs(34). For example, a study suggested that gastric cancer mortality rates have declined in the United States, which may be related to improved gastric cancer management and overall survival with the advent of more sophisticated surgical techniques and preoperative chemotherapy(35). The study found that European countries also had lower age-standardized incidence and mortality rates for gastric cancer globally. Probably due to the significant improvement of living conditions in European societies, survival rates have increased and morbidity and mortality have decreased through early detection, better access to care, and improved treatment(36–38).

The variation in age-standardized death and incidence rates of gastric cancer in different regions may be explained by the uneven or differential distribution of risk factors in different populations. Our results confirmed that a high-sodium diet plays an important role in the burden of gastric cancer. High salt concentrations directly damage the gastric mucosa, leading to hyperplasia of the pit epithelium and increasing the likelihood of endogenous mutations(39). In addition, high salt intake accelerates the process of intestinal metaplasia, which may lead to early gastric cancer(40). Previous studies have reported that a high sodium intake may alter the viscosity of the protective mucosal barrier and increase H. Helicobacter pylori, as a recognized risk factor for gastric cancer(41). Although people of all ages are at risk from a high-sodium diet, the age-standardized death (ASDR) and incidence (ASIR) rates of gastric cancer in different age groups show subtle differences under the influence of a high-sodium diet. Due to the gradual decline of body function and the decline of immunity, the elderly population is more sensitive to high-sodium diet, and the age-standardized mortality rate (ASDR) and incidence rate (ASIR) of gastric cancer were often more significant under the influence of high-sodium diet.

We also found that the age-standardized death and incidence rates of gastric cancer attributed to smoking show large geographical differences globally. Smoking remains a well-known risk factor for gastric cancer. Since 2005, with the implementation and promotion of the WHO Framework Convention on Tobacco Control, the prevalence of smoking has been steadily declining in most countries and regions(42),which is the reason for the decline in the contribution of smoking to the burden of gastric cancer in the past decade. However, in East Asia, 14.05% of age-standardized DALYs and 14.28% of age-standardized death were attributed to smoking, much higher than in other regions.

Healthy lifestyle guidelines generally recommend minimizing exposure to tobacco(43). Controlling potential risk factors, such as increasing tobacco control efforts, legislative measures to restrict the production and sale of tobacco products, raising public awareness of the dangers of smoking, promoting healthy lifestyles, and international cooperation to share research findings and best practices are among the ways to address gastric cancer in high-risk East Asian countries.

A major limitation of our study was that we selected only two risk factors for gastric cancer for analysis. The burden of gastric cancer can be attributed to other important risk factors, such as Helicobacter pylori infection. Gastric cancer is divided into cardia and non-cardia forms. Non-cardia gastric cancer is mainly associated with Helicobacter pylori infection and may be the main reason for the change in global gastric cancer incidence(44).Helicobacter pylori infection has not been studied due to limited information in the GBD database.

Gastric cancer has imposed substantial disease burdens globally and in different regions. Our study found that gastric cancer is causing a heavy burden of disease globally as well as in different regions and countries, with significant decreased in the incidence and mortality, particularly among women and in high SDI quintile. Mortality and DALY rates attributable to high sodium diet and smoking have generally declined. However, there are still significant differences between age groups and regions. Predictive models show an improvement in the disease burden of stomach cancer over the next decade. Targeted prevention and treatment strategies are still needed. Such as controlling smoking and increasing intake of fresh fruits and vegetables to reduce the risk of gastric cancer.

DALYs: Disability-adjusted life-years; ASIR: Age-standardized incidence rate; ASDR: Age-standardized death rate; ASR: Age-standardized DALY rate.

Ethics approval and consent to participate

Not applicable.

Consent for publication

Not applicable.

Availability of data and materials

GBD study 2021 data resources were available online from the Global Health Data Exchange (GHDx) query tool (http://ghdx.healthdata.org/gbd-results-tool).

Competing interests

The authors declare that they have no competing interests.

Funding

Not applicable.

Authors' contributions

Yangyan Fan collected the data, and contributed to writing the manuscript. Niping Qin conducted the literature search and data analysis. Zhiping Yang and Daiming Fan were responsible for the study design and the final revision of the manuscript. All authors have read and approved the final version of the manuscript.

Acknowledgements

We thank all the GBD Collaborators and team members for their valuable contributions and efforts, and the Institute for Health Metrics and Evaluation (IHME) for providing the data. We express our sincere gratitude to the Global Burden of Disease Study 2021 collaborators for their valuable contributions and efforts.

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No competing interests reported.

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The burden of Gastric Cancer and possible risk factors from 1990 to 2021，and projections until 2035: findings from the Global Burden of Disease Study 2021

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Introduction

Materials and Methods

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