Global trends of young- and late-onset gastric cancer

The global age-standardized incidence and mortality rate of gastric cancer declined from 22.44 and 20.48 per 100,000 in 1990 to 15.59 and 11.88 in 2019. For young-onset gastric cancer, the global incidence decreased from 2.20 per 100,000 population (95%UI: 2.04 to 2.36) in 1990 to 1.65 per 100,000 (95%UI: 1.52 to 1.79) in 2019, with AAPC of − 0.95 (95% CI − 1.25 to − 0.65, P < 0.001). Rates declined more in females (AAPC: − 1.31; 95% CI − 1.61 to − 1.02, P < 0.001) than males (AAPC: − 0.69; 95%CI − 1.14 to − 0.23, P = 0.003) (Table 1). Mortality rates also decreased from 1.61 per 100,000 population (95%UI: 1.49 to 1.72) in 1990 to 0.94 per 100,000 (95%UI: 0.87 to 1.02) in 2019 (AAPC: − 1.85; 95% CI − 2.15 to − 1.56, P < 0.001) (Table 1). Both sexes demonstrated significant decline in mortality rate over the past 30 years, with females having more pronounced decline than males (AAPC: − 1.99 vs. − 1.63) (Table 1).

Table 1 The incidence, mortality, and average annual percentage change (AAPC) of young and late -onset gastric cancer by sex and age from 1990 to 2019

Globally, late-onset gastric cancer incidence also decreased from 59.53 per 100,000 (95% UI: 55.70 to 63.13) in 1990 to 41.26 (95% UI: 38.49 to 48.08) in 2019 (AAPC: − 1.23; 95% CI − 1.39 to − 1.06, P < 0.001). Mortality rates of late-onset gastric cancer decreased from 53.58 per 100,000 (95% UI: 49.84 to 57.07) to 32.76 (95% UI: 29.37 to 35.79) in 2019 (AAPC: − 1.69, 95% CI − 1.79 to − 1.59; P < 0.001) (Table 1). There was a greater percent decline in incidence of late-onset compared to young-onset gastric cancer (30.7% vs. 25.0%, respectively), but not in mortality decline (38.9% vs. 41.6%, respectively). Over the past three decades, there was a general decline in the proportion of young-onset gastric cancer cases to all gastric cancer (Incidence proportion: 0.054 to 0.039; Mortality proportion: 0.045 to 0.029) (Fig. 1A), though this decline has plateaued since 2015.

Fig. 1

A The proportion of young-onset gastric cancer cases and deaths to total cases and deaths. B Annual male-to-female ratio change of incidence and mortality rate among young and late-onset gastric cancer

The male-to-female incidence rate ratio was generally higher in late-onset (range: 1.89–2.30) than young-onset gastric cancer (range: 0.96–1.29). However, due to a more rapid decline in gastric cancer incidence in females, the male predominance has been progressively increasing. The male-to-female incidence rate ratio increased from 1.01 in 1990 to 1.29 in 2019 for young-onset cancer, and from 1.77 in 1990 to 2.17 in 2019 in late-onset cancer. The increasing trends of male-to-female ratio on mortality rate are also noticed in both age groups (Fig. 1B).

Joinpoint regression analysis revealed substantial changes in the incidence trends of gastric cancer in 1997, 2002, and 2015. Notably, a significant decline was observed during two periods: from 1990 to 1997 (APC: − 0.70; 95% CI − 1.15 to − 0.26, P = 0.004) and from 2002 to 2015 (APC: − 2.38; 95% CI − 2.56 to − 2.20, P < 0.001). However, a slight increase in incidence rate of young-onset gastric cancer was observed from 1997 to 2002 (APC:0.60; 95% CI − 2.36 to 2.83; P = 0.219) and from 2015 to 2019 (APC: 1.39; 95% CI 0.06 to 2.74; P = 0.041; Fig. 2A). There was a consistent decrease in the incidence rate of late-onset cancer since 2004 (2004–2016 APC: − 2.05, 95% CI − 2.18 to − 1.91, P < 0.001; 2014–2019: APC: − 1.29, 95% CI − 1.67 to − 0.92, P < 0.001). A slight increase was noted between 1998 and 2004, but did not reach statistical significance (Fig. 2B).

Fig. 2

Joinpoint regression analysis comparison of global young-onset and late-onset gastric cancer incidence rate (A,B), and mortality rate (C,D), from 1990 to 2019. APC annual percentage change, AAPC average annual percentage change; *With significance, P < 0.05

Notable shifts in mortality rate trends of young-onset gastric cancer were noted in 1997, 2001, 2004, 2013, and 2016 (1990–1997 [APC − 1.08; 95% CI − 1.44 to − 0.72; P < 0.001], 2001–2004 [APC: − 2.90; 95% CI − 5.09 to − 0.67; P = 0.015], and 2004–2013 [APC: − 3.86; 95% CI − 4.13 to − 3.6; P < 0.001], which contributed to the overall decline. The 1997–2001 and 2016–2019 periods exhibited a slight increase in mortality but were not statistically significant (Fig. 2C). Late-onset gastric cancer demonstrated similarly notable joinpoints as the incidence rate trend decreased in 1993, 1998, 2004, 2007, and 2015, with a significant decrease in mortality rate from 2004 (2004–2007 APC: − 3.36, 95% CI − 4.25 to − 2.73, P < 0.001; 2007–2015 APC: − 2.55, 95% CI − 2.67 to − 2.23, P < 0.001; 2015–2019 APC: − 0.79, 95% CI − 0.92 to − 0.67, P < 0.001) (Fig. 2D). Detailed global incidence and mortality rates of young-onset and late-onset gastric cancer by year from 1990 to 2019 are shown in Supplementary Table 1.

Trend of young- and late-onset gastric cancer by regions and nations

The global distribution of gastric cancer incidence rates in 2019 and the AAPC for incidence rates from 1990 to 2019 are shown in Fig. 3.

Fig. 3

World map of incidence rate in 2019 and AAPC of incidence from 1990 to 2019 for young and late-onset gastric cancer

Based on the WHO region classification, the Africa region depicts the steepest decrease of young-onset gastric cancer incidence, from 0.99 per 100,000 population (95% UI: 0.83–1.12) in 1990 to 0.61 (95% UI: 0.51–0.73) in 2019, with AAPC of − 1.67 (95% CI − 1.76 to − 1.59, P < 0.001). However, the Western Pacific region showed a non-significant decrease in incidence (AAPC: − 0.03; 95% CI − 0.52 to 0.48, P = 0.921), while the region of the Americas showed a non-significant increase (AAPC: 0.08; 95% CI − 0.18 to 0.34, P = 0.551; Table 2). Mortality rates of young-onset gastric cancer decreased in all six WHO regions.

Table 2 The incidence rate, cases, and average annual percentage change (AAPC) of young and late-onset gastric cancer according to regional stratification from 1990 to 2019

In contrast, a significant decrease in both incidence and mortality rates were observed across all WHO regions for late-onset gastric cancer. The European region demonstrated a significant decrease in both incidence (AAPC: − 1.76; 95% CI − 2.10 to − 1.42, P < 0.001) and mortality rate (AAPC: − 2.22; 95% CI − 2.55 to − 1.88, P < 0.001) (Table 2 and Supplementary Table 2), while the Eastern Mediterranean Region exhibited the least decline in incidence (AAPC: − 0.84; 95% CI − 0.95 to − 0.79, P < 0.001) and mortality rates (AAPC: − 1.04; 95% CI − 1.11 to − 0.97, P < 0.001) over the past three decades.

When different GBD regions were examined, most regions reported a decreasing incidence of young- or late-onset gastric cancer (Table 2). However, Central Latin America (AAPC: 0.30; 95% CI 0.11–0.63, P = 0.005), East Asia (AAPC: 0.70; 95% CI 0.26–1.32, P = 0.030), and Oceania (AAPC: 0.17; 95% CI 0.06–0.29, P = 0.003) reported a significant increase in young-onset gastric cancer incidence rate. Moreover, an increase in mortality rate (AAPC: 0.18; 95% CI 0.08–0.29, P = 0.001) was observed in young-onset gastric cancer in Oceania (Supplementary Table 2).

When stratified by individual nations, Cyprus (AAPC: 2.02; 95% CI 1.14–2.91, P < 0.001) and Lesotho (AAPC: 1.92; 95% CI 1.36–2.49, P < 0.001) exhibited the most significant rise in the incidence rates of young-onset cancer (Table 3). At the same time, Lesotho (AAPC: 1.89; 95% CI 1.59–2.19, P < 0.001) and Zimbabwe (AAPC: 1.62; 95% CI 0.93–2.33, P < 0.001) were found to have the largest increase in mortality rates of young-onset cancer (Supplementary Table 3). Cyprus and Lesotho, the two countries with the most significant increases in young-onset gastric cancer incidence rates, also exhibited a significantly increase in incidence rate of late-onset cancer (AAPC: 0.42, P = 0.004 and AAPC: 0.34, P < 0.001 respectively) (Table 3). As for late-onset cancer, Dominican Republic demonstrated the most increase in incidence rate (AAPC: 1.07; 95% CI 0.12–2.03, P = 0.028). United States Virgin Islands observed the largest increase in mortality rate (AAPC: 0.98; 95% CI 0.71 to 1.25, P < 0.001) (Supplementary Table 3). Andorra, Cyprus, Guam, Australia, San Marino, and Canada were countries (or subnational administrative area) with high SDI but low-level AAPC in both young- and late-onset cancer. In contrast, Ethiopia, and Rwanda were countries with low SDI but high AAPC for young- and late-onset gastric cancer (Supplementary Fig. 1). A detailed list of the countries with significant increased incidence and mortality rates is shown in Table 3 and Supplementary Table 3.

Table 3 List of countries with significantly increased average annual percentage changes of young and late-onset gastric cancer incidence rate

China, with the world's largest population during the study period, was the only East Asia country that showed a significant increase in the incidence rate of young-onset gastric cancer over the study period (AAPC: 0.84; 95% CI 0.30–1.39, P = 0.002) according to either GBD or UNSD [28] geographical region criteria (Supplementary Fig. 2). Furthermore, the Joinpoint analysis results among the three most populous countries (China, India and the United States of America) indicate a significant increase in young-onset gastric cancer incidence rates in China after 2014 (APC: 4.06, 95% CI 2.00–6.15, P = 0.001) and in India after 2016 (APC: 2.50, 95% CI 0.47–4.58, P = 0.020), respectively. However, no similar trend was observed for late-onset gastric cancer in these countries (Fig. 4). The fluctuations in the incidence and mortality rate of young-onset gastric cancer in the U.S. remained relatively stable over past three decades. Among the three most populous countries, the U.S. exhibited the slowest decline in incidence (AAPC: − 0.02, 95% CI − 0.55 to 0.51, P = 0.947), but the most rapid decline in mortality (AAPC: − 1.13, 95% CI − 1.35 to − 0.91, P < 0.001) (Fig. 4).

Fig. 4

Joinpoint regression analysis comparison of China, India, and the United States of America for young and late-onset gastric cancer incidence rate. APC annual percentage change, AAPC average annual percentage change; *With significance, P < 0.05

In terms of the exposure to carcinogens associated with young-onset gastric cancer in China, it was found that young individuals from China had significantly higher levels of smoking exposure (SEV: 8.50–9.68) compared to the global average (6.34–9.50). For high sodium diets, despite a decline in the global average SEV from 49.39 in 1990 to 43.27 in 2019, young individuals in China have consistently maintained a relatively stable level of exposure to high-sodium diets (94.97–96.70). Moreover, alcohol consumption in China experienced a significant increase from 2005 and has exceeded the global average since 2012 (Supplementary Fig. 3).

Sensitivity analysis

Japan and the Republic of Korea, both countries with a significant burden of gastric cancer, have implemented national screening programs for individuals over 40 years old. Both countries exhibited an overall decline in incidence and mortality rates from 1990 to 2019 for both young and late-onset gastric cancers. For late-onset cancer, the decline in incidence (AAPC: − 2.05 vs. − 1.21) and mortality (AAPC: − 3.82 vs. − 0.92) was more pronounced in the Republic of Korea than in Japan. Moreover, there has been a significant increase in both incidence (2016–2019 APC: 2.40, 95% CI 0.46–4.37, P = 0.018) and mortality rates (2016–2019 APC: 95% CI 0.82, 95% CI 0.15–1.49, P = 0.021) in Republic of Korea after 2016 for late-onset cancer, which was not observed in Japan (Supplementary Fig. 4A). For young-onset gastric cancer in these two countries, the Republic of Korea had higher incidence and mortality rates than Japan. While Japan experienced a greater decline in incidence rates (AAPC: − 3.44 vs. − 2.32), the reduction in mortality was steeper in the Republic of Korea (AAPC: − 4.03 vs. − 5.01). Similar to late-onset cancer, there was a non-significant increase in young onset gastric cancer incidence observed in Republic of Korea after 2016 (APC: 3.43, 95% CI − 2.12 to 9.30, P = 0.213) (Supplementary Fig. 4B). Also, when compared the ratio of young-onset gastric cancer incidence rates in the Republic of Korea and Japan with global incidence rates, it was found that the burden of gastric cancer in the Republic of Korea remains high globally, with an increasing trend observed after 2016 (from 2.72 to 2.78) (Supplementary Fig. 5).

After excluding data from these two countries with universal screening, the decline in global incidence rate (AAPC: − 0.99, 95% CI − 1.15 to − 0.83, P < 0.001) and mortality rate (AAPC: − 1.68, 95% CI − 1.78 to − 1.58, P < 0.001) of late-onset gastric cancer was still observed but at a lower magnitude (AAPC: − 1.23 and − 1.69 respectively) (Supplementary Fig. 6).

When considering different cutoff ages for young-onset gastric cancer, a significant decline in the incidence and mortality rates of young gastric cancer was still observed between 1990 and 2019 with cutoff values of 30 or 50 (All P value for AAPC < 0.05). However, there has been a consistent decrease in both incidence and mortality since 2010 with these cut-offs, instead of the observed increase in incidence rate from 2015 with cut-off age of 40 years. (Supplementary Figs. 7, 8).

Trend of young- and late-onset gastric cancer according to SDI

According to the SDI quintiles, the most significant decrease in incidence rate was observed in the high SDI quintile, both for young-onset (AAPC: − 2.33, 95% CI − 2.61 to − 2.04, P < 0.001) and late-onset gastric cancer (AAPC: − 1.53, 95% CI − 1.33 to − 1.73, P < 0.001) (Table 2). For both age groups, the mortality rate decreased significantly in all five SDI quintiles (Supplementary Table 2).

The incidence and mortality rates of young-onset gastric cancer did not exhibit a significant decline with increasing SDI (AAPC of incidence rate Slope: − 0.11, P = 0.13; AAPC of mortality rate, Slope: − 0.75, P = 0.101) (Fig. 5A and B). However, there was a significant decline in both the AAPC of incidence rate (Slope: − 0.20, P = 0.004; Fig. 5C) and mortality rate (Slope: − 0.38, P < 0.001; Fig. 5D) of late-onset gastric cancer with increase in the country’s SDI. Higher SDI countries had a more rapid decline of incidence or mortality rate of late-onset gastric cancer from 1990 to 2019.

Fig. 5

Correlation of average SDI with AAPC of incidence and mortality rate in young and late-onset gastric cancer. AAPC average annual percentage change, SDI Sociodemographic Index