Changing trends of disease burden of gastric cancer in China from 1990 to 2019 and its predictions: Findings from Global Burden of Disease Study

Introduction

Gastric cancer (GC) is a malignant tumor that causes serious disease burden, being the fifth most commonly diagnosed cancer and the third cause of death (1,2). In 2018, there were more than 1,033,701 new cases of GC and an estimated 782,685 deaths from it, worldwide (3). China is a high incidence region of GC (4). According to the 2018 global cancer statistics, 456,124 new GC cases and 390,182 deaths were estimated to have occurred in China, accounting for 44.1% and 49.9% of the cases worldwide, respectively (3). The high incidence and mortality in China highlight the urgency of preventing and treating GC.

GC is a multifactorial disease that can be caused by both environmental and genetic factors (5). Some of these factors are not modifiable (such as age, gender, and family genetic history), while others are potentially modifiable (such as smoking, alcohol consumption, and poor dietary habits) (5,6). These potentially modifiable factors make it possible to prevent and control the incidence of GC. Helicobacter pylori (H. pylori) infection is the main risk factor for the development of GC (7). The population infection rate of H. pylori is approximately 50% (8,9), while only about 1% of infected cases eventually develop into GC (9). Unhealthy lifestyles, such as smoking and alcohol consumption, also have been found to have a significant association with an increased risk of developing GC (5,6). In addition, dietary factors, such as the intake of salty food and low consumption of fruits and vegetables, may increase the risk of GC development (5). Moreover, sex is also a significant risk factor for GC (5,10), and the differences between the sexes may be attributed to their different lifestyles and dietary habits (5). Therefore, it is of great importance to develop prevention and control strategies for GC according a person’s sex.

China is one of the largest developing countries and has rapid economic growth. As the economy develops, people’s lifestyles and dietary factors change accordingly. It is important and necessary to understand the epidemiological trends and patterns of GC in China, as this is essential for formulating relevant prevention strategies to improve public health. The latest Global Burden of Diseases (GBD) study (2019) provides extensive data on the incidence, mortality, and disability-adjusted life-years (DALYs) of GC from 1990 to 2019, which made it possible for us to understand the disease burden of GC in China. Therefore, in this study, using the latest data of the GBD study (2019) in China, we comprehensively evaluated the national disease burden of GC and its temporal trends in relation to age, sex, and risk factors; and also predicted the numbers and rates of GC incidence and mortality in the next 25 years. Our research results should improve our understanding of the disease burden of GC, help us evaluate the effectiveness of current prevention strategies, and provide a more scientific basis for promoting the establishment of prevention strategies.

Materials and methods

Results

Discussion

China is one of the countries with the highest burden of GC in the world (13,24). In the past, few studies analyzed the burden of GC in China (24-26), and the latest disease burden of GC is still unknown. Therefore, in our study, using the latest data of the GBD study (2019), we did a more comprehensively and in-depth analysis of the disease burden of GC and its temporal trends by age, sex, and risk factors, and uniquely, we predicted the numbers and rates of incidence and mortality in the next 25 years in China. First of all, in 2019, there were 612.82 thousand new cases and 421.54 thousand deaths attributed to GC in China, and the ASIR and ASMR were 30.64 per 100,000 and 21.72 per 100,000, respectively. In our study, the numbers and rates of incidence and deaths in 2019 were higher than those estimated by the International Agency for Research on Cancer (IARC) and related studies in China; the reasons for these differences might be related to the difference in reporting years (reported in 2018 and 2015, respectively), the coverage points of data collection, and the estimation models.

China contributes the largest numbers of GC incident cases, deaths and DALYs, worldwide (13). The numbers of incident cases, deaths and DALYs all significantly increased from 1990 to 2019 in China among the total population, and our model predicted the numbers of new cases and deaths of GC should continue to increase in the next 25 years in both sexes. Meanwhile, the rates of incidence, mortality and DALYs showed an overall decreasing trend in the past three decades among the total population, which is consistent with previous studies (25,26). Although the rates of incidence and mortality of GC showed downward trends in the world and China, the disease burden of GC in China is still heavy (25) and these rates are higher than the average levels of the world (27).

Many factors produced the high disease burden of GC in China. Firstly, China has the largest population in the world, with a population of approximately 1.42 billion, accounting for almost one-fifth of the world’s population (28-30). The large population base contributes to higher numbers and rates of incidence, mortality and DALYs, which can have a significant impact on the world (29). Meanwhile, China is transforming into an aging nation (31,32). This trend may cause the numbers and rates of incidence, mortality and DALYs to be concentrated in the elderly population (especially ≥60 years old), which is consistent with our results. Secondly, China has operated a screening program for the populations with a high risk of GC (25), and significant improvement has been made in the early diagnosis and treatment of GC (24). A series of screening and early detection programs have been formulated and implemented by the Chinese government since 2005 (26,33,34). These programs were first implemented in 11 high-risk regions in China, and then expanded to all provinces in 2019 (34). The target population of the current screening program is 40−69 years old of both sexes (26). The implementation of screening and early detection programs might be an important explanation for our results. The improvement of medical conditions and the implementation of public health strategies and screening programs would result in a decline in the rates of mortality and DALYs of GC, and on the other hand, the detection rate of new cases would increase, thereby keeping the incidence rate from declining substantially. However, it is expected from the prediction model that the future incidence rate will steadily decrease. Thirdly, with the improvement of public health and the changing of lifestyles in China (35), the risk factors (such as smoking, alcohol consumption, a high-sodium diet and H. pylori infection) have been effectively controlled, leading to a decline in the rates of mortality and DALYs. Lastly, the improvements in socioeconomic status might be also an important reason (26). The rapid economic development of China (especially in the past 10 years) has greatly improved the living standards of residents and their personal awareness of diseases, which might have resulted in a decline in the rates of incidence, mortality and DALYs in our study. In summary, the large population base, aging of the population, implementation of screening and early detection programs, controlling risk factors, and improvements in socioeconomic status, together contribute to the high disease burden of GC in China.

Although the overall decreasing trends in the rates of incidence, mortality and DALYs were observed in all age-specific groups and both sexes, these indicators showed a short-term upward trend from 2000 to 2010. The screening and early detection programs were initially implemented in 2005 in China (34), which might have led to an increase in the detection of the number of new cases in the following years. The other possible reason for this observed result might be that China had implemented a series of prevention strategies, including tobacco-control strategies since 2005 (36,37) and a salt-consumption program since 2007 (38). In addition, an increase in death-data collection points might also be a reason. The deaths data were reported by the China Disease Surveillance Points system: 145, 161 and 605 disease surveillance points were used from 1991 to 2003, 2004 to 2012, and 2013 to 2017, respectively (15); from 2008 to 2017, all the deaths data were reported through the online reporting system of the Chinese Center for Disease Control and Prevention (15).

We further found that the risk factors of smoking and a high-sodium diet played an important role in the GC burden, and might also be the main cause of differences between males and females. Smoking is one of the well-known risk factors, and the GC burden caused by smoking is different between males and females. In our study, the proportion of DALYs attributable to smoking was about 10 times higher in males than females. In China, the smoking prevalence rates of males and females were 52.9% and 2.4% in 2010, respectively (39,40), which may be an important reason for the gender differences. Moreover, in 2010, the prevalence of GC was the highest among males in the 45-64 years age group (63.0%) (40), which may increase the burden of disease for males over 45 years old in the future. Consistent with our speculation, we observed higher proportions of DALYs of GC attributable to smoking in males in the 50-94 years age group (>25%) in 2019. China has formulated many tobacco control strategies and mobilized all people to participate (36,37,41). The WHO Framework Convention on Tobacco Control (FCTC) was ratified by China in 2005, and tobacco control has made progress during the past decade (36,37). A slight downward trend in the proportion of DALYs attributable to smoking was observed in our study. The mechanisms of the effect of smoking on GC are unclear currently. Overall, smoking is associated with the development of precursor lesions of GC; in addition, tobacco smoke contains a variety of chemical carcinogens (especially nitrosamines and other nitroso compounds) (42,43). These chemical carcinogens may bind to DNA and affect the normal function of DNA, eventually leading to GC (42,43).

High-salt consumption is an important risk factor for GC and may increase the risk of it through the following mechanisms. Firstly, high-salt consumption may irritate the gastric mucosa, inducing intestinal metaplasia, and lead to atrophic gastritis (44,45). Secondly, high-salt consumption can promote the carcinogenesis progress of gastric dysplasia or GC among person infected with H. pylori (44-46). Moreover, high-salt foods (such as salted fish, preserved foods and processed meats) may also contain nitrate and nitrite, which may promote the formation of N-nitroso compounds (44). From our study, we found that the proportion of DALYs attributable to a high-sodium diet was more than 8.7% in China in 2019; and a slightly downward trend in the proportion of DALYs attributable to a high-sodium diet was observed among males and females. Since 2007, China developed the “China Healthy Lifestyle for All” initiative to improve people’s health literacy, which includes important content about the control of salt intake (38). With the control of salt-consumption program, the rates of death and DALYs attributable to a high-sodium diet has slightly decreased in the past three decades. However, the GC burden caused by a high-sodium diet is still relatively high. Therefore, more comprehensive prevention and control measures should be taken to further reduce the burden of GC caused by high-salt intake.

We should discuss other important risk factors for GC that were not contained in the database. H. pylori is a well-known risk factor for GC, and is classified as a class I human carcinogen (47,48). In our study, although we could not evaluate the GC burden caused by H. pylori, we could speculate that the proportion of DALYs attributable to H. pylori infection might be high. In 2015, about 4.4 billion people worldwide were H. pylori-positive (49). In the Western world, the prevalence of H. pylori has greatly decreased, while in developing countries, the prevalence of H. pylori is still at a high level (49). The prevalence of H. pylori is 55.8% in China, which is higher than in Japan (51.7%) and Korea (53.9%) (49). In China, because of wider population-based screening (28), increased awareness of the treatment of H. pylori infection (28), the development of an effective vaccine (50), and the improvement in socioeconomic status, the prevalence of H. pylori shows a decreasing trend (decreased 0.9% annually) (51), which may contribute to the decrease in the rates of mortality and DALYs. In addition, other reported risk factors for GC include alcohol consumption, infection with the Epstein-Barr virus, socioeconomic status, a low intake of fruits and vegetables, obesity and gastroesophageal reflux disease, poor oral health, radiation, and a family history of GC (5,52-54).

There are some limitations in our study. Firstly, we only assessed the disease burden of GC at the national level and could not conduct a more detailed assessment at the provincial level. Secondly, we could not divide GC into the cardia GC and non-cardia GC. The temporal trend of the incidence and risk factors for these two subtypes of GC are different (5,52). Smoking, age, sex, radiation and family history are common risk factors for both types of GC; while obesity and gastroesophageal reflux disease are specific risk factors for cardia GC; H. pylori infection, low socioeconomic status and a high-salt diet are associated with an increased risk of non-cardia GC (5,53). Thirdly, we could not evaluate the GC burden caused by other important risk factors because the GBD database does not contain the corresponding data. Fourthly, since the data were a summary of several sites, the limitation of report omission might exist, which might result in the underestimation of our results. Although the data used to estimate incidence and mortality in the GBD study were fitted, filled, and corrected through various models, including a linear step mixed-effects model and spatiotemporal Gaussian process regression, our findings are consistent with those of previous studies. However, we should not ignore the fact that the proportion of the population covered by these systems has changed during the past three decades, which needs to be fully considered when interpreting our results.

Conclusions

We provide a comprehensive analysis of the burden of GC in China. During the past three decades, benefitting from the implementation of prevention strategies and the improvement of medical technology, the rates of incidence and mortality decreased. However, the number of new cases and deaths increased and will further increase in the next 25 years due to the aging population and high-risk behaviors (such as smoking, a high-sodium diet and H. pylori infection). Therefore, focusing on the risk factors, more detailed prevention and control strategies should be formulated for males and females and people in different age groups. Further effort is also needed to mobilize the entire population to participate, which may have a positive effect on variations in the incidence of GC. On the other hand, strategies and measures for improving the level of early diagnosis and developing new treatment techniques should be proposed to reduce the mortality of GC.

Acknowledgements

This study was supported by the National Key Research and Development Program of China (No. 2017YFC0907003); the National Natural Science Foundation of China (No. 81973116 and 81573229); and the Joint Research Funds for Shandong University and Karolinska Institute (No. SDU-KI-2020-03).

Footnote

Conflicts of Interest: The authors have no conflicts of interest to declare.