Chinese and global burdens of gastric cancer from 1990 to 2019

Abstract Background Gastric cancer is a common cancer in China. This project investigated the disease burden of gastric cancer from 1990 to 2019 in China and globally. Methods The global age‐standardized rates (ASRs) were extracted from the Global Burden of Disease. Moreover, the estimated annual percentage changes (eAPCs) in the ASRs of incidence (ASIR), mortality (ASMR), and disability‐adjusted life‐years (DALYs) were calculated to determine the trends by countries and regions. Results In China, the ASIR declined from 37.56 to 30.64 per 100,000 and the ASMR declined from 37.73 to 21.72 per 100,000. The global ASIR decreased from 22.44 to 15.59 and the ASMR declined from 20.48 to 11.88 per 100,000 persons from 1990 to 2019. The ASIR was the lowest in Malawi (3.28 per 100,000) and the highest in Mongolia (43.7 per 100,000), whereas the ASMR was the lowest in the United States of America (3.40 per 100,000) and the highest in Mongolia (40.04 per 100,000) in 2019. The incidence of early‐onset gastric cancer increased in China. The DALYs attributed to gastric cancer presented a slight decrease during the period. China had a higher mortality/incidence ratio (0.845) and 5‐year prevalence (27.6/100,000) than most developed countries. Conclusion China presented a steady decline in the incidence and mortality rates for gastric cancer. The global ASIR, ASMR, and DALYs showed a slight rise decrease. Different patterns of gastric cancer rates and temporal trends have been identified in different geographical regions, indicating that specific strategies are needed to prevent the increase in some countries.

accounted for 44.21% of the total number. 3 Gastric cancer is the second most frequently diagnosed cancer and the second leading cause of cancer-related deaths in China. 4 The disease burden of gastric cancer in China is high. Comparison of the gastric cancer metrics and trends in China and other countries is of great value for developing various health policies. Moreover, reports on the spatial distribution and trends in gastric cancer would help policy makers allocate resources properly.
In this study, we extracted age-standardized rates (ASRs) for gastric cancer from the Global Burden of Disease (GBD) study. The trends of ASRs could be a surrogate for the changing disease patterns and reflect the shift in risk factors. The estimated annual percentage changes (eAPCs) are broadly used to measure time trends in ASRs. To provide an updated picture of epidemiological trends and geographic patterns of gastric cancer, we considered temporal variations in incidence, mortality rates, disability-adjusted life-years (DALYs), and APCs according to age, sex, and region in China and the world.

| The Global Burden of Disease Project
The Global Burden of Disease (GBD) project presents the cancer incidence, mortality, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life-years (DALYs). 3 The GBD project collected and analyzed the data for more than 350 diseases and injuries in 195 countries. The Global Health Data Exchange (GHDx) online data source query tool 5 provides comparisons by age, sex, age groups, and geography from 1990 till date. This project helps visualize health trends over time as well as develop cancer control strategies to achieve global targets and improve equity in cancer care.
We collected the incidence, mortality, and DALYs of gastric cancer, and measured ASRs from 1990 to 2019 according to sex, five socio-demographic indices (SDI), 21 regions, and 195 countries/territories. The five SDI categories (low, low-middle, middle, high-middle, and high SDI) are also described by the GBD project 2017. 6 The ASRs per 100,000 person-years are calculated using WHO world standard population. 7

| Statistical analyses
We gleaned data from the GBD database to examine the epidemiology trends in gastric cancer from 1990 to 2019. Only the age-specific rates in 2019 were incorporated into the study. The ASRs from GBD were calculated using the WHO world standard population.
The estimated APCs were calculated as follows: Where x refers to the calendar year. The R program (R x3.5.1) was used for statistical analyses and preparing the plots.
The global incident cases of gastric cancer went upward from 883,400 cases (95% UI = 834,240 to 929,170 cases) in 1990 to 1,269,810 cases (95% UI = 1,150,490 to 1,399,820 cases) in 2019, corresponding to an increase of 43.74% (Table 1). The incident cases in all SDI quintiles went upward. The low-middle SDI quintile had the highest increase of 73.15%, whereas the high-SDI quintile had the lowest increase of 4.48% (Table 1).

| Disease burden of gastric cancer
Gastric cancer led to a heavy health burden in China. Gastric cancer was attributable to 22 Figure 2E), which showed a more significant decrease in females (eAPC = −0.58, 95% CI = −0.67 to −0.44) (Table S1).

| Age-specific rates of gastric cancer in
China and the world in 2019 Figure 3 illustrates the age-specific incidence, mortality rates, and DALY of gastric cancer in China and the world in 2019.
Overall, the age-specific rates in China were well above the global level for each age group. In China, the incidence and mortality rates rose in parallel with age in 2019. The incidence in younger age groups (0-29 years) was less than 5/100,000, increasing sharply after 55 years. Considering the high fatality rate of gastric cancer in China, similar tendencies were observed in the age-specific mortality rates. For patients younger than 40 years, the mortality rates were less than 5/100,000, which increased sharply after 60 years.  The age-specific DALY rate reached a high point of 1,529.10/100,000 in the 75-79 year age group (Table S3). The incidence of gastric cancer was significantly higher in males than in females among all age groups. In the subgroup analysis of gender, the age-specific incidence and mortality rates increased with age. The age-specific incident rates reached the peak in the 80+ year age group for both genders (435.05/100,000 for males, 161.65/100,000 for females). The mortality rates were similar to the incident rates, being higher in males. The age-standardized DALY for males peaked in the 75-79 year age group (2173.53/100,000, 95% CI=1,951.28-2,394.77/100,000), while it reached the peak at 80+ year age group in females (1,069.07/100,000, 95% CI=874.32-1,188.01/100,000) (Table S3; Figure 3A, 3C and 3E).

| Age-specific trends in the incidence of gastric cancer in China
General trends of gastric cancer in China are shown in Figure 1A. However, there was a significant difference between genders and age groups. There was a worrisome rise in  Table S5). In the subgroup analysis of gender, young men (15-49 years) were the only group to have increased incidence (eAPC = 0.54, 95% CI = 0.14-1.10). (Table S5).

| DISCUSSION
This study presented a comprehensive review of the gastric cancer burden over the last 29 years based on the latest national estimated data worldwide. This study shows a gradual decline in ASIR, ASMR, and age-standardized DALYs in China and the world from 1990 to 2019, as well as demonstrating the variations by age and gender in China. What stands out is the V-shaped changing trends in ASRs for the period of 1990-2005, which are quite different from the global trends. We suggest that this phenomenon is associated with the development of cancer registration in China. The National Central Cancer Registry (NCCR) of China was founded in 2002, acting as the national bureau for the management of cancer registration. 8 Data quality of cancer registration was not high during the period of 1990-2002. There is a potential bias in the ASRs in early period.
The ASIR of gastric cancer indicated a gradual decline during the study period. In more than half of the countries examined, gastric cancer is likely to reach rare cancer thresholds by 2035. 9 The new cases of gastric cancer kept rising year-onyear, but the age-standardized incidence rate showed a downward trend in China and the world. The aging and growth of the population can explain the above phenomena.
Our results highlight a worrisome feature of a consistent increase in the incidence of early-onset gastric cancer (EOGC) among the young population in China. The result has already been observed in both high-incidence and lowincidence countries. 9,10 Most early-onset patients presented a worse prognosis than late-onset gastric cancer patients. 10,11 Since younger individuals have less exposure to environmental carcinogens than older ones, genetic factors may play a more relevant role in EOGC than in traditional gastric cancer. This public health issue requires monitoring in the future. Further studies are needed to investigate the cause of the increasing incidence of EOGC.
Most studies reported 1.8-2.0 times higher risk of gastric cancer in men than in women. 12,13 In agreement with prior studies, our study indicated that males are 1.10-3.0-fold more likely to have gastric cancer than females. In agreement with prior studies, our study found that the incidence of gastric cancer was 2.2-2.5 times higher in males than in females in the past decade. Such differences could be attributed to lifestyle (men are more likely to be influenced by cultural reasons and take up drinking and smoking than are women 14 ), environmental or occupational exposures, and physiological differences. [15][16][17] Moreover, the incidence and mortality rates decreased among both sexes in China. The decreasing trends of ASIR and ASMR were more pronounced in females. The control and prevention strategies for gastric cancer in males need to be strengthened. 18,19 Some risk factors, such as drinking, smoking, obesity, and unhealthy diet, increases the incidence levels of gastric cancer. 20,21 Excessive consumption of salty, pickled, preserved, and fried foods (which are rich in N-nitroso compounds) in East Asian cultures, are proved to generate higher gastric cancer risk. 22,23 Besides, H. pylori (Helicobacter pylori) is a contributing factor for gastric cancer. The risk of developing gastric cancer in individuals infected with H pylori is at least two times higher than those who test negative. 24 During the last decade, the incidence of gastric cancer has decreased steadily owing to the reduction in risk factors in China and other countries. 25 The decline benefits from better food preservation associated with refrigeration during transport and storage. The increasing consumption of fresh fruit and vegetables also plays a vital role in bringing about the observed decline in the incidence of gastric cancer. 26,27 It is now clear that the decreasing trend in gastric cancer occurrence is parallel to the decline in H. pylori infection in both Eastern and Western populations. [28][29][30][31] Powerful measures for tobacco control decreased the incidence of gastric cancer. 32,33 The downward trend in mortality might be linked to several reasons. First, treatment for H. pylori eradication has a positive influence on the mortality of gastric cancer. 28,34,35 In some prospective studies, vitamin supplementation (Vitamin C and E) or garlic was associated with the reduced mortality of gastric cancer. 28,29 Besides, an advanced understanding of gastric cancer helps clinicians to treat the disease and reduce mortality effectively. The selective screening programs for high-risk populations carried out in the high-risk regions significantly reduce the mortality rates in China. 36,37 Geographical variation in the incidence and mortality rates remains high across the world. High ASIR of gastric cancer have been reported in East Asia and High-income Asia Pacific, whereas Africa and North America present low ASIR. Specific dietary patterns of the East Asian population mentioned above may account for the extremely high incidence within this region. Owing to effective screening strategies, the ASMR values in Japan and South Korea are much lower than those in other countries, despite the high ASIR. 38,39 One critical point that should be emphasized here is that the completeness of the data and the cancer registries in African countries might differ significantly from the countries with high HDI; therefore, these factors might introduce a bias in the results and interpretations. So the disease burden in these regions is possible to be underestimated.
DALYs is a comprehensive indicator which reflects the disease burden. 2,4 Because of the high incidence of gastric cancer and its large population, China is a major contributor to the global gastric cancer burden. From 1990 to 2019, the age-standardized DALYs decreased more pronounced in women than in men in China. These data suggest that sex is an important factor affecting gastric cancer disease burden. 19 On top of the above findings, there might be the following limitations in this paper that can be improved further. First, non-cardia and cardia gastric cancer demonstrate remarkable characteristics in the epidemiology and risk factor profiles. 40 Because of the incomplete cancer diagnostic and registration practices, subsite-specific analysis of gastric epidemiology was not performed in this study. Second, we are not able to perform further analysis due to the lack of details regarding gastric cancer (such as classification, staging, and treatment received).

| CONCLUSION
This study outlined the Chinese and global burdens of gastric cancer from 1990 to 2019. The ASIR, ASMR, and DALYs have decrease in China and the world. However, rates and temporal trends varied substantially by gender, age, socioeconomic status, and geography. The incident and mortality rates are relatively high in China. Moreover, there was a worrisome rise in the incidence of early-onset gastric cancer in China. Specific strategies are needed to reduce the disease burden of gastric cancer.