2.1 Data sources

The data on cancer incidence and mortality used in this study were sourced from the GLOBOCAN 2022 online database (https://gco.iarc.fr/en) [15]. GLOBOCAN, a project led by the International Agency for Research on Cancer (IARC), provides national estimates for cancer incidence, mortality, and prevalence by site and sex across 185 countries and territories, covering 36 different cancer types [3]. All age-standardized incidence and mortality rates (ASIR and ASMR) in GLOBOCAN 2022 were calculated using the world standard population as a reference [3].

Data on DALYs attributable to cancers in China, the US, and the UK for the years 1990 and 2021 were sourced from the GBD 2021 online results tool (https://www.healthdata.org/research-analysis/gbd) [16], developed by the Institute for Health Metrics and Evaluation (IHME). The GBD project annually estimates mortality, years of life lost, years of life lived with disability, and DALYs by age and sex for 88 risk factors and combinations across 204 countries and territories and 811 subnational locations [17]. In this study, we presented estimates of DALYs per 100,000 population in 2021 for 32 cancer sites in China, the US, and the UK, categorized by sex and age. We also displayed percentage and rank changes in all-age and age-standardized DALY rates from 1990 to 2021 to highlight trends in the cancer burden across these countries. All age-standardized DALY rates were calculated using the GBD reference population [17].

The ASIRs and ASMRs of cancer for trend analysis were obtained from the Global Health Data Exchange (GHDx) (https://ghdx.healthdata.org/) via the GBD results tools repository (https://vizhub.healthdata.org/gbd-results/). The search parameters were “total cancers”, “tracheal, bronchus, and lung cancer”, “breast cancer”, “colon and rectum cancer”, “liver cancer”, “cervical cancer”, “stomach cancer”, “prostate cancer”, and “esophageal cancer” for cause; “incidence” and “deaths” for measurements; “China”, “United States of American”, and “United Kingdom” for location; “1990-2021” for years; “rate” for metrics; “male, female and both” for sex; and “age-standardized” for age.

2.2 Statistical analysis

The joinpoint regression analysis is an effective method for analyzing trends over time to identify the time points in which the trend significantly changes. Therefore, we employed Joinpoint regression models [18] to analyze the temporal trends in ASIRs and ASMRs for selected cancer sites across China, the US, and the UK from 1990 to 2021. Using Joinpoint software (version 4.8.0.1; National Cancer Institute, Rockville, MD, US), we systematically assessed the time trends and identified statistically significant shifts between joinpoints. The models allowed for up to 3 segments (2 join-points). To quantify the direction and extent of these trends, the annual percent change (APC) was calculated. A trend was described as either “increasing” or “decreasing” when the slope (APC) significantly deviated from zero. The statistical significance of the trend was determined by examining their 95% confidence intervals (CIs). An APC with a 95% CI greater than zero was interpreted as a significant upward trend, whereas an APC with a 95% CI less than zero was considered a significant downward trend. If the 95% CI included zero, the ASIR or ASMR was considered stable. A P value of less than 0.05 was considered to indicate statistical significance.

3.1 Cancer incidence and mortality patterns in China, the US, and the UK

According to estimates from GLOBOCAN 2022, there were 19,976,499 new cancer cases (including non-melanoma skin cancer) diagnosed globally in 2022. Nearly 24.2% of these cases (4,824,703) were reported in China, comprising 2,533,906 males and 2,290,797 females. The ASIR for all cancers in China was 201.6 per 100,000 population (Supplementary Table S1). Males exhibited a higher ASIR compared to females (209.6 vs. 197.0 per 100,000 population, respectively). When both sexes are combined, lung cancer had the highest ASIR (40.8 per 100,000 population), followed closely by breast cancer (33.0 per 100,000 population; data pertains to females only), thyroid cancer (24.6 per 100,000 population), colorectal cancer (20.1 per 100,000 population), liver cancer (15.0 per 100,000 population), cervical cancer (13.8 per 100,000 population), stomach cancer (13.7 per 100,000 population), prostate cancer (9.7 per 100,000 population), and esophageal cancer (8.3 per 100,000 population; Figure 1A and Supplementary Table S1). Notably, in 2022, digestive cancers (including colorectal, stomach, liver, and esophageal cancers) accounted for 30.4% of all cancer cases diagnosed in China.

As detailed in Supplementary Table S2, approximately 2,574,176 individuals in China died from cancer (including non-melanoma skin cancer) in 2022, representing 26.4% (2,574,176 out of 9,743,832) of all cancer deaths globally. The ASMR for all cancers in China was 96.5 per 100,000 population. Men experienced an ASMR nearly 46.8% higher than that of women (127.5 per 100,000 population for men vs. 67.8 per 100,000 population for women). Lung cancer was the leading cause of cancer mortality, with an ASMR of 26.7 per 100,000 population, followed by liver cancer (12.6 per 100,000 population), stomach cancer (9.4 per 100,000 population), colorectal cancer (8.6 per 100,000 population), esophageal cancer (6.7 per 100,000 population), breast cancer (6.1 per 100,000 population), and cervical cancer (4.5 per 100,000 population; Figure 1A and Supplementary Table S2). Notably, the ASMR for digestive cancers was significantly higher compared to cancers from other systems.

In 2022, there were significant differences in cancer incidence and mortality between China, the US, and the UK. The ASIR for all cancers in China (201.6 per 100,000 population) was similar to the global average (196.9 per 100,000 population) but lower than that in the US (367.0 per 100,000 population) and the UK (307.8 per 100,000 population; Supplementary Table S1). However, the ASMR in China was significantly higher than that in the US but slightly lower than that in the UK (96.5 per 100,000 population in China compared to 82.3 per 100,000 population in the US and 98.3 per 100,000 population in the UK; Supplementary Table S2). The combined proportion of lung, breast, colorectal, and prostate cancers in China (42.9% of all new cases) was comparable to that in the US (37.4%) and the UK (47.1%; Supplementary Table S1). Unlike in the US and UK, where breast and prostate cancers were the most prevalent, lung and colorectal cancers were the most common in China (Supplementary Table S1). Cancers such as liver, stomach, esophageal, and cervical were more frequently diagnosed in China (22.8% of all new cases) than in the US (4.3%) and the UK (6.0%; Supplementary Table S1). These cancers accounted for 31.9% of all cancer deaths in China, whereas they were responsible for less than 12% of cancer deaths in either the US or UK (Supplementary Table S2).

Figure 1B and C summarized the top 10 cancer types by ASIR and ASMR for males and females across China, the US, and the UK in 2022. Lung and colorectal cancers were among the five most frequently diagnosed cancers for men in all three countries. However, Chinese men had significantly higher incidences of liver, stomach and thyroid cancers compared to their counterparts in the US and UK. Conversely, the ASIRs for prostate cancer, bladder cancer, and leukemia were higher among men in the US and UK than in China. For women, breast, lung, and colorectal cancers were the most common across the three countries. Chinese women showed a higher likelihood of developing thyroid and cervical cancers, while women in the US and UK had higher incidences of corpus uteri tumors. Notably, both men and women in China had higher ASMRs for stomach and liver cancers compared to those in the US and UK.

3.2 Temporal trends of cancer incidence and mortality in China, the US, and the UK

The time trend analysis in cancer incidence data from GHDx between 1990 and 2021 revealed that the ASIR for all cancers in Chinese men increased from 256.3 per 100,000 population in 1990 to 283.2 per 100,000 in 2011, followed by a period of stabilization until 2019 and a significant increase from 2019 to 2021 (Table 1). The ASIR for all cancers in Chinese women showed an upward trend until 2008, followed by a slight decrease until 2016, and then a notable rise between 2016 and 2021 (Table 1). However, the ASIR trends of all cancers in the US are quite different from that in China. Both sexes experienced a slight increase in ASIR from 1990 to 2000, followed by a sharp rise between 2000 and 2004/2005, and finally, a steady decline from 2004/2005 to 2021 (Table 1). Unlike China and the US, the ASIR for all cancers in the UK showed an overall downward trend from 1990 to 2021. For men in the UK, the ASIR remained relatively stable until 2016, and for women in the UK, until 2014. After these points, both sexes experienced a significant decline in ASIR through 2021 (Table 1). Additionally, the ASMR for both men and women in all three countries showed a significant decline during the study period, with the exception of Chinese men, who experienced a notable increase between 1997 and 2003 (Table 1).

During the same study period, notable variations in cancer incidence trends were observed among China, the US, and the UK (Table 2). For lung cancer, the ASIRs were lower for women than for men in all three countries. In 1990, the ASIR for lung cancer in men was higher in the US and the UK than in China, but it rapidly declined throughout the study period, eventually falling far below the ASIR in China. For women, although the US initially had the highest lung cancer ASIR and experienced a significant increase from 1990 to 2000, it has since been on a downward trend, reaching 32.5 per 100,000 population in 2021. However, the ASIR for lung cancer in Chinese women saw significant increases during 1990-2005 and 2015-2021. Similarly, the ASIR for breast cancer and prostate cancer in the US was the highest, but after a brief increase between 1990 and 1994/1995, it began to decline sharply. In contrast, the ASIR for these cancers in China was initially much lower but then rose significantly. For colorectal cancer, the ASIR for both men and women in the US began to decrease rapidly from 2002 and 2001, respectively, while in China, it maintained a rapid upward trend throughout the whole study period. However, although the ASIRs for colorectal cancer in men and women of the UK experienced brief increases (2004-2007 for men in the UK and 2002-2019 for women in the UK), it showed a significant decline for most of the time during the study period. It's important to note that the ASIRs for liver cancer in China showed an overall downward trend during the entire study period. Although the ASIR for liver cancer in Chinese men experienced slight increases between 1990-2001 and 2004-2021, there was a sharp decline from 2001 to 2004. For Chinese women, the ASIR for liver cancer generally decreased, with the exception of a slight increase between 2008 and 2016, whereas in the US and UK, these rates of both sexes remained significantly increased throughout the study period. The overall ASIR of stomach cancer exhibited a downward trend in all three countries, particularly in China. As for esophageal cancer, the ASIR showed an overall decline in China, while it remained relatively stable in the US and the UK. Conversely, the ASIR for cervical cancer in China showed a downward trend before 1999, but then rose from 10.4 per 100,000 population in 1999 to 13.4 per 100,000 in 2021, while a sharp decline in cervical cancer ASIR was observed in both the US and the UK during the same period (dropping from 16.7 to 12.6 per 100,000 population in US, while dropping from 16.4 to 10.3 per 100,000 population in UK).

As summarized in Table 3, the ASMR trends of lung, liver, stomach, and esophageal cancers for all three countries were generally consistent with their ASIR trends. In breast cancer, the ASMR in the US and the UK sharply declined throughout the study period, while the ASMR in China did not change significantly. A similar pattern was also observed in prostate cancer. Unlike the steadily decreasing ASMR of colorectal cancer in the US and the UK, the ASMR for colorectal cancer in Chinese men remained largely unchanged overall. However, in Chinese women, the ASMR gradually increased after a slow decline from 1990 to 2014. Regarding cervical cancer, the ASMR in the US and the UK generally followed a downward trend throughout the study period, whereas, the ASMR in China first sharply declined between 1990 and 1999, then sharply increased until 2003, after which it began to decrease significantly again.

3.3 Cancer burden in China, the US, and the UK

In 2021, the GBD study estimated that cancers were responsible for 71,037,170 DALYs in China (Supplementary Table S3). The highest cancer-related DALY burden in China was attributed to lung cancer, accounting for 18,920,203 DALYs (26.6% of all cancer-related DALYs), followed by stomach cancer (10,642,127 DALYs; 15.0%), esophageal cancer (6,898,666 DALYs; 9.7%), colorectal cancer (6,848,390 DALYs; 9.6%), and liver cancer (4,890,023 DALYs; 6.9%). Together, these five cancers contributed to over 67% of the total cancer DALY burden in China.

Figure 2 highlights that leukemia and cancers of the brain and central nervous system were the leading causes of cancer burden among children and adolescents under 20 years of age in China. For young adults (20-44 years) and middle-aged men (45-59 years) in China, liver, lung, and stomach cancers were the most significant contributors, with lung and stomach cancers remaining predominant in older men (60 years and above). In young and middle-aged Chinese women, lung, breast, stomach, and cervical cancers were the top contributors to cancer burden, whereas lung, stomach, colorectal, and breast cancers were the most burdensome in older women.

The cancer burden varied significantly between China, the US, and the UK in 2021. China exhibited a higher age-standardized DALY rate for all cancers compared to the US and UK, with rates of 3459.8, 2932.2, and 3075.3 per 100,000 population, respectively (Supplementary Table S3). In China, the populations bearing the highest cancer burden were generally younger than those in the UK (Figure 2). Lung cancer was the leading cause of cancer burden in all three countries (Supplementary Table S3). Besides lung cancer, the top cancer burden contributors for China included digestive cancers—specifically stomach, esophageal, colorectal, and liver cancers—whereas in the US and UK, colorectal, breast, pancreatic, and prostate cancers were more prominent (Supplementary Table S3). Regarding the age distribution of DALY, leukemia and cancers of brain and central nervous system were the top contributors among children and adolescents in all three countries (Figure 2). For young men, liver and lung cancers led to the highest DALY in China, while in the US and UK, colorectal cancer and brain and central nervous system cancers were more significant (Figure 2). In young women, breast and cervical cancers were the leading cause of DALY in the US and UK, but breast and lung cancers were predominant in China (Figure 2). For middle-aged men, the top cancer burden contributors were lung and colorectal cancers in the US and UK, but those in China were lung and stomach cancers (Figure 2). In middle-aged women, lung and breast cancers were the leading cause of DALY in all three countries (Figure 2). Among the elderly, lung cancer remained the most significant contributor to the DALY burden across all three countries (Figure 2).

3.4 Shifts of cancer burden in China, the US, and the UK

From 1990 to 2021, China saw a 32.7% reduction in its age-standardized DALY rate, dropping from 5141.9 (95% uncertainty interval [UI] = 4517.0-5783.8) per 100,000 population in 1990 to 3459.8 (95% UI = 2902.3-4122.9) per 100,000 in 2021. This decline was more pronounced in females (38.1%) than in males (28.8%). Figure 3 outlines the shifts in all-age DALY rates for 32 different cancer types in China. By 2021, lung cancer had become the leading contributor to the DALY burden, overtaking stomach cancer, which held that position in 1990. Colorectal cancer, liver cancer, breast cancer, cervical cancer, and prostate cancer rose in the rankings, becoming the fourth, fifth, sixth, tenth, and seventeenth leading causes of DALY burden, respectively. In contrast, the burden of stomach cancer declined. It fell by 18.3%, leading to a drop in its rankings—from first to second. Meanwhile, the rankings for esophageal cancer remained stable, despite a 51.4% decrease in its age-standardized DALY rate, respectively, over the same period.

The trends in the cancer burden of the US and the UK during this period differed notably from those in China (Figure 3). While lung, colorectal, and breast cancers remained the top 3 cancers contributing to the DALY burden in both countries, their all-age and age-standardized DALY rates saw substantial declines over the past 31 years. The most significant change was observed in liver cancer, with all-age DALY rates increasing by 183.8% in the US and 215.7% in the UK, resulting in its ranking rising from nineteenth to ninth in the US and from nineteenth to seventh in the UK. Additionally, the age-standardized DALY rate for cervical cancer dropped sharply, particularly in the UK, where it fell by 61.3% between 1990 and 2021, causing it to drop out of the top 20 causes of DALY burden by 2021, down from fourteenth in 1990.