Gastric Cancer Risk among Immigrants and Socioeconomic Groups in the Netherlands

Gastric cancer presents a significant global health challenge, exhibiting considerable regional variability in incidence. Annual age-standardized incidence rates in East Asia (16.1 per 100,000) are far higher than those in Western Europe (5.6 per 100,000; ref. 1). The modest overall incidence in Western countries poses challenges to the balance between the harms and benefits of population-based screening and prevention programs. As a result, gastric cancer often presents at advanced stages with high rates of metastases and poor clinical outcomes (2). Gastric cancer therefore remains a substantial cause of cancer mortality, causing 95,431 deaths annually in Europe alone (1). To address this challenge, the European Commission has invited member states to implement gastric cancer prevention programs in regions with a high disease burden (3, 4). The effectiveness of such programs may be improved by concentrating on high-risk groups in the population.

Identification of high-risk demographic groups could facilitate targeted gastric cancer screening in countries with low gastric cancer incidence. Because the majority of gastric cancer cases can be attributed to the infectious agent Helicobacter pylori (5), individuals in populations subgroups with a higher H. pylori prevalence are likely to be at elevated risk of gastric cancer. Such increased risk was previously observed among specific ethnic minority groups in the United Kingdom (6), the United States (7–9), Canada (10, 11), Scandinavia (12–14), Australia (15) and Germany (16). In the Netherlands, it has been suggested that first-generation migrants from the Antilles, Morocco, Surinam, and Turkey face an elevated gastric cancer risk (17). However, it is unclear whether other immigrant groups and second-generation immigrants also face an increased risk. Moreover, a recent study demonstrated that individuals of lower socioeconomic status (SES) face an elevated gastric cancer risk in the Netherlands (15). The interplay between SES and immigration history in influencing gastric cancer risk also remains poorly understood. A comprehensive understanding of which groups are at an increased risk and the magnitude of this risk could help prioritize prevention interventions more effectively.

We therefore aimed to identify groups at a high gastric cancer risk and assess their risk using individual-level population data on migration history and SES.

Cases of invasive gastric cancer [according to the International Classification of Diseases (ICD) ICD-O3: C16] diagnosed between 2010 and 2022 were obtained from the Netherlands Cancer Registry (NCR). The analysis encompassed overall gastric cancer as well as stratification into topographic subgroups cardia (ICD C16.0) and noncardia gastric cancer (ICD C16.1–16.6), as these two groups are recognized to have distinct natural histories and risk factors (18). Cancer stage was based on the tumor–node–metastasis classification at the year of diagnosis. Histologic type by the Lauren classification was available from 2015 onward. Use of NCR data has been approved by the Dutch Upper Gastrointestinal Cancer Group.

Cancer data were integrated with the Personal Records Database from Statistics Netherlands using sex, dates of birth and death, and postal code. Based on these data, all patients with cancer were merged to record identification numbers as used by municipal registries to manage personal data. As every resident in the Netherlands is registered in a population registry, this database holds personal data for the entire Dutch population.

First-generation immigrants were defined as individuals born outside the Netherlands. Country of birth was used as a proxy for the ethnicity of these immigrants and investigated for the 14 largest immigrant groups in the Netherlands at the time of study. Second-generation immigrants were defined as individuals who were born in the Netherlands but with at least one parent born outside the Netherlands. Following the definitions of Statistics Netherlands, ethnicity of second-generation migrants is determined by the country of birth of the mother unless she was born in the Netherlands, in which case the father’s country of birth is used (19). In addition to analyses on the 14 largest immigrant groups, all world countries were also grouped into regions based on the geographical definition provided by the United Nations also used by the Global Cancer Observatory (20).

Financial wealth was used as a proxy for SES, using household-level data from Statistics Netherlands (21). A household’s financial wealth was based on both standardized income and capital. After ranking households based on income and capital, their wealth was calculated by summing their cumulative share of total income and their cumulative share of capital, following the standardized methods of Statistics Netherlands (21). Individuals were then ranked according to their household’s wealth and assigned an SES score from 1 (lowest) to 5 (highest), corresponding to quintiles of financial wealth per household. SES scores were calculated from 2014 onward, as data on financial wealth were only available from that time onward.

Incidence rates for each first-generation immigrant and socioeconomic group were calculated by dividing the incident cases by the life-years in the subgroup. These rates were age-standardized using the European Standard Population (22), consistent with the approach adopted by the NCR. The time span of the incidence rates for immigrant groups was the period 2010 to 2021, given that the registration for 2022 was not finalized at the time of analysis. Incidence rates per socioeconomic group were calculated for the period 2014 to 2021, given that SES scores were available from 2014 onward. Odds ratios (OR) and corresponding 95% confidence intervals (CI) for developing gastric cancer associated with ethnicity and SES were derived through multivariable logistic regression using data from all individuals in our dataset. The outcome variable was a case if an individual was diagnosed with gastric cancer in the period 2010 to 2022 and a noncase if not. In addition to analyzing all gastric cancer cases collectively, models and corresponding ORs were also constructed with gastric cancer stratified by location (noncardia vs. cardia) as an outcome variable.

In examining ethnicity, separate regression analyses were conducted per country and world region. All ORs were controlled for age and sex. ORs associated with ethnicity were generated both controlled and uncontrolled for SES. The uncontrolled ORs may be useful for differential diagnoses, whereas the controlled estimates provide a more accurate assessment of association between ethnicity and gastric cancer risk. Due to data availability, ORs controlled for SES could only be calculated for the population from 2014 onward.

All analyses were conducted using Stata 18 and R version 4.2.1.

All data were anonymized and analyzed in the secure environment of Statistics Netherlands. The data that support the findings of this study are available from Statistics Netherlands and the Dutch Cancer Registry (NCR). Restrictions apply to the availability of these data, which were used under license for this study. Data are available with the permission of Statistics Netherlands and the NCR.

A total of 21,299 incident gastric cancer cases were recorded in the NCR between 2010 and 2022. Of these patients, the median age (IQR) was 72 (16) and 13,822 (65%) were male. Noncardia tumors were most prevalent, accounting for 10,240 cases (48%), followed by cardia tumors at 6,567 (31%). Lauren classification was recorded for 11,839 cases from 2015 onward, with 4,779 (40%) intestinal type cases, 4,158 (35%) diffuse type cases, and 2,902 (25%) registered as mixed, indeterminate, or unknown. Most gastric cancer cases were diagnosed at late stages III (2,895 cases, 14%) and IV (9,587 cases, 45%).

Of all cases in the NCR, 18,264 (86%) were successfully linked to data from Statistics Netherlands. The uncoupled patients that could not be linked had a similar distribution as the coupled patients in terms of age, sex, and year of diagnosis. Among the linked cases, 16,051 (88%) patients were born in the Netherlands compared with 2,213 (12%) born abroad. Among those born in the Netherlands, 949 (6%) were second-generation immigrants. Of the 14,081 patients with gastric cancer diagnosis after 2013, SES could be derived for 13,933 patients (99%). Gastric cancer was found to be more prevalent in the lowest SES quintile (on a scale of 1–5), with 3,816 (27%) cases occurring in individuals with the lowest SES compared with 1,716 cases (12%) in those with the highest SES. Further detailed descriptive statistics, categorized by topographic location, are presented in Table 1.

Figure 1 shows the age-standardized incidence rates of gastric cancer stratified by topographic location grouped per country (Fig. 1A) and region (Fig. 1B) of birth in the period 2010 to 2021. All crude and age-standardized incidence rates can be found in the Supplementary Material (Supplementary Table S1).

Immigrant populations with a significantly higher risk of gastric cancer were identified. The odds of developing gastric cancer were significantly higher for individuals born in Bosnia–Herzegovina (OR, 2.42; 95% CI, 1.78–3.29); Turkey (OR, 2.22; 95% CI, 1.99–2.48); China (OR, 1.92; 95% CI, 1.40–2.65); Afghanistan (OR, 1.92; 95% CI, 1.33–2.77); Surinam (OR, 1.68; 95% CI, 1.48–1.90); Morocco (OR, 1.63; 95% CI, 1.43–1.86); and the Dutch Antilles (OR, 1.61; 95% CI, 1.30–2.00) compared with the general population (Fig. 2). These ORs were controlled for age, sex, and SES. The increased odds of overall gastric cancer could mainly be attributed to noncardia tumors. Specifically, the ORs for developing noncardia gastric cancer were higher than those of overall gastric cancer for all high-risk countries of birth. Populations at increased risk for cardia gastric cancer were not identified (Fig. 2). ORs uncontrolled for SES were generally slightly higher than ORs controlled for SES, suggesting that only a limited fraction of the increased cancer risk among immigrants can be attributed to variations in SES (Supplementary Figs. S1 and S2).

Regression using world region as an explanatory variable showed that people born in Western Asia (OR, 2.00; 95% CI, 1.81–2.23), Southern Europe (OR, 1.83; 95% CI, 1.57–2.14), East Asia (OR, 1.75; 95% CI, 1.35–2.26), Western Africa (OR, 1.59; 95% CI, 1.16–2.22), South America (OR, 1.62; 95% CI, 1.44–1.82), the Caribbean (OR, 1.59; 95% CI, 1.29–1.96), and Northern Africa (OR, 1.55; 95% CI, 1.37–1.77) were at a significantly higher risk of developing gastric cancer compared with the general population, controlled for age, sex, and SES (Fig. 3). Again, these differences were driven by a higher risk of noncardia gastric cancer. Differences in stage distribution and age patterns were not observed across immigrant and Dutch-born populations (Supplementary Fig. S3; Supplementary Table S2).

Populations of second-generation immigrants were not observed to be at higher risk for developing gastric cancer, noncardia gastric cancer, or cardia gastric cancer (Fig. 4; Supplementary Figs. S4–S6). Second-generation immigrants were generally younger than first-generation immigrants in our study period (Supplementary Tables S3 and S4).

Gastric cancer incidence was higher in individuals with a lower SES (Fig. 5A). A SES below five was significantly associated with an increased odds of developing gastric cancer compared with a SES of 5, with an OR (95% CI) of 1.48 (1.39–1.57) in individuals with the lowest SES compared with those with the highest SES (Fig. 5B). This association was even more pronounced for noncardia gastric cancer, with an OR (95% CI) of 1.75 (1.61–1.90) versus an OR of 1.05 (0.95–1.15) for cardia cancer (Fig. 5B). Differences in stage distribution by SES were not observed (Supplementary Fig. S7). Odds were slightly lower when controlled for immigration status but significant across the same strata (Supplementary Fig. S8).

Our population-based study has demonstrated that certain first-generation immigrant populations in the Netherlands have a higher risk of gastric cancer compared with individuals born in the Netherlands. This risk was observed in people born in western and eastern Asia, Southern Europe, western and northern Africa, South America, and the Caribbean. Low SES was also observed to be a risk factor for gastric cancer. Nevertheless, even after controlling for SES, immigrants remained at an elevated risk. Second-generation immigrants did not exhibit a heightened risk profile for gastric cancer.

The increased risk of gastric cancer among first-generation immigrants seems likely due to a greater H. pylori prevalence in the country of origin. As the immigrant groups at increased risk were typically born in countries with a high prevalence of H. pylori (23) and infection often occurs at young ages (24), first-generation immigrants are likely to be infected before migrating. Consequently, they remain at increased risk of gastric cancer despite moving to a low-risk area such as the Netherlands. A higher risk among immigrants parallels patterns in other cancers linked to infectious agents, such as hepatocellular carcinoma (hepatitis B) and cervical cancer (human papillomavirus; refs. 25, 26). Prevalence of H. pylori may also explain why higher gastric cancer risk among second-generation immigrants in the Netherlands was not observed. When born in the Netherlands, where H. pylori prevalence is relatively low (23), their risk of infection is probably lower than that of first-generation immigrants.

Our findings are consistent with prior research. An earlier study examined gastric cancer risk among the five largest immigrant groups in the Netherlands during 1997 to 2009 (17). Immigrants born in Turkey exhibited the highest risk with a standardized incidence ratio (95% CI) of up to 1.8 (1.5–2.3). Although our estimated OR of 2.16 for Turkish first-generation immigrants falls within this CI, their results suggest a slightly lower risk in immigrant populations. These minor discrepancies could arise from variations in metrics and differences in demographics over time (27). A recent systematic review also revealed a heightened gastric cancer risk in immigrant populations, ranging from 1.08- to 5.05-fold compared with the reference population (28). Again, our results align with this spectrum. Consistent with our findings, that review reported that second-generation immigrants were at lower gastric cancer risk than first-generation immigrants. A statistically significant higher risk was observed in three of the six studies reporting on this group. Notably, the previous studies typically lacked control for SES and provided only relative metrics for a limited number of first-generation immigrant groups. In contrast, our study offers estimates controlled for SES and presents incidence rates per group for immigrants from diverse countries and regions. In terms of stage distribution, we did not observe differences by immigration status or SES, similar to prior findings from Norway (29). This may be the result of the relatively good access to care among most population subgroups in Norway and the Netherlands.

One of the main strengths of our study is the use of nationwide individual data, enabling us to identify high-risk groups for gastric cancer that are often underrepresented in clinical studies (30–32). Through the integration of NCR data with the Personal Records Database data, we conducted an in-depth investigation on the background of more than 18,000 patients with gastric cancer. Moreover, the comprehensiveness of our data facilitated detailed analyses, such as examining age-specific incidence and assessing stage distributions. Finally, our multivariable analyses allowed us to take multiple factors into account simultaneously. This is an advantage compared with previous studies on gastric cancer that were unable to control for SES.

Nonetheless, our study has several limitations. First, conducting survival analyses using hazard rates may have provided insights into disease risk patterns over time. However, our analysis was primarily focused on identifying risk factors for cancer occurrence rather than the timing of its development. Also, the lack of time-to-event data and the rarity of gastric cancer as an outcome make logistic regression a more suitable choice (33). Second, the count of second-generation immigrants over the age 40 surpassed 10,000 solely for three regions in our dataset. Accordingly, second-generation immigrants may not have reached an age in which gastric cancer has sufficient incidence to demonstrate any differential. Therefore, our analysis cannot definitely rule out an increased risk among second-generation immigrants, warranting future follow-up investigations. Furthermore, data on SES were only available from 2014 onward and were determined exclusively based on wealth. Whereas Statistics Netherlands also collects data on recent employment history and education, we opted to exclude these factors from our analysis, as their corresponding scores diminish substantially at higher ages. Incorporating employment history and education would therefore have substantially decreased the age distribution in groups with a high SES, which could have introduced bias. Finally, country of birth may not fully capture ethnic identity and can overlook ethnic diversity within individuals born in the same country. However, country of birth provides an objective measure and enables a differentiation between first- and second-generation immigrants. This approach may have practical and ethical advantages over other socially constructed classifications, like perceived race or ethnicity (34).

Our findings emphasize the importance of gastric cancer prevention within high-risk groups, even in low-incidence countries. Recently, the European Commission recommended that member states should follow screen-and-treat strategies for H. pylori in countries and regions with a high gastric cancer incidence (3, 4). We identified immigrant groups in which age-standardized incidence rates of more than 20 per 100,000 were observed. These rates surpass those seen in the highest-risk European countries, such as Estonia (13.1 per 100,000) and Portugal (12.8 per 100,000; ref. 1). Alongside prevention efforts in high-incidence countries, we therefore advocate for targeted gastric cancer prevention and screening initiatives tailored to specific high-risk groups within low-risk countries. Screen-and-treat strategies for H. pylori in immigrant populations could be considered. Moreover, primary care physicians may opt for earlier H. pylori testing or referral of high-risk patients for gastroscopy, facilitating the detection of cancers at earlier stages. Further research should investigate which targeted prevention strategies are effective and cost-effective.

In conclusion, certain first-generation immigrants remain at an elevated risk for gastric cancer despite migration to a low-risk region. Identification of these high-risk groups should be used to facilitate targeted gastric cancer prevention. Potential benefits of targeted H. pylori test-and-treat strategies in immigrant populations should be explored in clinical and modeling studies. Primary care physicians should be cognizant of high-risk immigrant and socioeconomic groups, facilitating the early detection of cancer within these vulnerable populations.

D.T. Mülder reports grants from the European Commission during the conduct of the study. H.J. van de Schootbrugge-Vandermeer reports grants from the European Commission during the conduct of the study. R.H.A. Verhoeven reports grants from Bristol Myers Squibb and other support from Daiichi Sankyo outside the submitted work. I. Lansdorp-Vogelaar reports grants from the European Commission during the conduct of the study. No disclosures were reported by the other authors.

D.T. Mülder: Conceptualization, data curation, software, formal analysis, investigation, visualization, methodology, writing–original draft, project administration, writing–review and editing. H.J. van de Schootbrugge - Vandermeer: Validation, investigation, methodology, writing–review and editing. J.F. O’Mahony: Conceptualization, supervision, validation, investigation, visualization, methodology, writing–review and editing. D. Sun: Validation, investigation, writing–review and editing. W. Han: Validation, investigation, writing–review and editing. R.H.A. Verhoeven: Investigation, methodology, writing–review and editing. M. van Loo: Methodology, writing–review and editing. W. van de Veerdonk: Methodology, writing–review and editing. M.C.W. Spaander: Conceptualization, funding acquisition, validation, investigation, writing–review and editing. I. Lansdorp-Vogelaar: Conceptualization, supervision, funding acquisition, validation, investigation, methodology, writing–review and editing.

This project has received funding from the European Union program EU4Health under Grant Agreement No 101101252. R.V.A. Verhoeven received research grant from Bristol Meyers Squibb and consultancy fee from Daiichi Sankyo, all paid to the institution. M.C.W. Spaander received research support from Medtronic, Sysmex, and Sentinel.