Stomach Cancer Incidence and Mortality Trends among Circumpolar Nations

This article is featured in Highlights of This Issue, p. 811

In 2018, stomach cancer was the fifth most commonly diagnosed cancer worldwide with over a million new cases (1). It is the third most common cause of cancer-related death and is responsible for 783,000 deaths per year globally (1). Incidence rates are higher among men compared with women and highest among older adults (2). Rates vary by geography and are highest in Eastern Asia and Eastern Europe, while relatively lower in North America and Northern Europe (1). The global burden of stomach cancer disproportionately affects Indigenous populations versus their non-Indigenous counterparts (3). There are two major topographical subsites that differ in rates and risk factors: noncardia and cardia stomach cancer (4). Globally, the attributable fraction of cases due to Helicobacter pylori (H. pylori) is greater among noncardia (89%) compared with cardia stomach cancers (17.8%; ref. 5). Noncardia stomach cancer incidence rates have declined in many populations due to prevention efforts such as detection and treatment of H. pylori and improvements in food preservation (1). In contrast, stomach cardia cancer incidence has increased in high-income countries. Important risk factors for cardia cancers include obesity and gastroesophageal reflux disease (1, 6).

There are 27 circumpolar regions among eight nations: Canada, the United States, Denmark (including self-governing Greenland and Faroe Islands), Finland, Iceland, Norway, Sweden, and Russia (7). Stomach cancer rates in most circumpolar nations have declined in the past few decades (8–10). However, despite improvements in survival, stomach cancer remains a highly fatal cancer–the five-year net survival is 28% in Canada (8).

Although incidence and mortality rates have declined overall across circumpolar nations, the burden of stomach cancer is not distributed equally (11, 12). In the United States, incidence and mortality rates were reported to be higher among non-Hispanic American Indian and Alaska Native (AIAN) people compared with the US non-Hispanic White (USW) population (11, 13). In Canada, stomach cancer incidence was elevated among Indigenous people in Northwest Territories compared with non-Indigenous people (14). In Yukon, stomach cancer mortality was elevated compared with national rates (15). In Greenland, stomach cancer rates were elevated compared with Nordic Countries overall (16). Disparities within some circumpolar subpopulations are linked to regional differences in sociodemographic characteristics and risk factors such as H. pylori infection (17). The purpose of this descriptive study was to provide a comprehensive and up-to-date assessment of stomach cancer incidence and mortality trends among circumpolar nations and regional populations using population-based data and discuss trends in relation to regional risk factors.

Young and colleagues defined circumpolar regions as the northern-most regions of circumpolar nations (Alaska; the three northern territories of Canada; the northern counties of Norway, Sweden, and Finland), island states in the North Atlantic (Greenland, Iceland, and Faroe Islands), and 13 regions of the Russian Federation (Table 1; Fig. 1; refs. 7, 18).

Northern-most regions of circumpolar countries are unique in terms of sociodemographics, environmental conditions, and social determinants of health (7, 19). They also have a larger proportion of Indigenous peoples (Table 1). For many Indigenous populations, such as Inuit, Sami, Aleut, and Athabaskan peoples, traditional territories extend beyond international borders (7, 18–20). Indigenous people in Greenland are of Inuit descent (7, 16) and call themselves Kalaallit in Greenlandic (18). Inuit peoples also include the Yupik and Inupiat of Alaska and Russian Chukotka region (21). The traditional territories of Sami people include parts of northern Norway, Sweden, Finland, and the Kola Peninsula in Russia (22). In Russia, there are 47 Indigenous groups recognized by federal law and defined as “people who live on their traditional ancestral territories, adhere to their original way of life, and believe themselves to be independent ethnic entities, with a population under 50,000 people” (18, 23).

In addition, circumpolar populations are often widely dispersed, small, and experience intense physical environments (7). Together, these contribute to unique health burdens and systems relative to national counterparts (24, 25). Despite most circumpolar countries being at the top of the human development index (HDI; ref. 26), north-south health gradients have been reported within these countries (7, 19). Further health disparities exist between Indigenous and non-Indigenous counterparts within northern regions (7, 25). North-south gradients are more apparent in the United States and Canada. Among Nordic countries, Greenland performs lower than regional counterparts (e.g., Denmark; refs. 7, 19, 20). In Russia, Northern regions show worse health indicators than the rest of the country (7, 19).

Data on invasive stomach cancer (C16 as per the International Classifications of Diseases for Oncology, Third edition; ref. 27) were derived from national publicly funded sources that conform to the International Agency for Research on Cancer reporting standards. This included the Canadian Cancer Registry (28), Canadian Vital Statistics (29), US WONDER (30–32), NORDCAN (33), and CI5plus (Cancer Incidence in Five Continents) database (34). In Russia, regional data were obtained from the database of the Northwestern Federal District for eight regions, and for Russia as a whole, the national reports on cancer incidence and mortality (35, 36), and the Russian Fertility and Mortality database (37). The St. Petersburg, Karelia, and Arkhangelsk cancer registries were included in Cancer Incidence in Five Continents (CI5) series (34). Data sources and variables used in this analysis are described in Supplementary Table S1.

The direct method was used to calculate age-standardized incidence (ASIR) and mortality rates (ASMR) per 100,000 person years (PY; ref. 38). Rates were standardized to the World (WHO 2000–2025) standard (39). For Canadian incidence data, counts were randomly rounded to the nearest 0/5/10th. Annual counts in Canada's North were small (often less than 5) and random rounding had a relatively greater impact on ASIRs compared with other regions. Therefore, incidence data for Canada's North was examined for both sexes combined. For ASMRs and mortality-to-incidence ratios (MIR), the 2011 Canadian standard was used because Canadian regional age-specific cancer mortality data were not available. For Canadian, Nordic, and Russian estimates, standard errors used to approximate 95% exact confidence intervals were derived from the gamma distribution using the epitools package in R (40). For U.S. estimates, SEs were queried from CDC WONDER, which also uses the gamma distribution (41).

Rates were stratified by sex, time period, region, and Indigenous ethnicity (reported as AI/AN race for U.S. data only). Indigenous statistics were not available from non-U.S. cancer registries as it is not routinely collected or reported (42). Rates were examined using ten-year rolling periods to remove some of the variability resulting from small northern population sizes. Rates were suppressed if they had less than 16 cases to protect privacy and limit reporting of unreliable estimates.

Incidence standardized rate-ratios (SRR) were calculated by dividing the ASIR of a given subpopulation and the ASIR of its corresponding nation or major region (e.g., Northern Canadian males ASIR divided by Canadian males ASIR, which includes Northern Canadian male cases). For U.S. estimates, Indigenous ASIRs were examined in relation to the regional White ASIRs. Nordic subpopulations were compared with Nordic countries overall. Confidence intervals for SRRs were approximated using Smith method (38). MIRs were calculated by dividing ASMRs by ASIRs for corresponding regions.

To assess trends in incidence and mortality, SRRs were calculated by dividing the ASIR or ASMR of the most recent period (2007–2016) to the ASIR or ASMR of the earliest period (1999–2008). An SRR greater or lower than 1.0 with nonoverlapping 95% confidence intervals was considered to show an increase or decrease, respectively. An SRR with 95% CIs overlapping 1.0 were considered to be stable.

SD choropleth maps were produced to examine the distribution of incidence SRRs. Shapefiles were derived from Statistics Canada (43), US Government Census State geography shapefiles (44), and the International Agency for Research on Cancer (IARC) provided shapefiles for Nordic countries. Greenland's shapefile was retrieved from the New York University Spatial Data Repository (45). Russia's shapefile was obtained from the Database of Global Administrative Areas (46).

Ethics approval was obtained from the University of British Columbia–Children's and Women's Hospital Research Ethics Board (H17–01539). Approval for publication was also obtained from the Alaska Native Tribal Health Consortium.

Ten-year rolling ASIRs were plotted by regional population and sex (Fig. 2A and B). Supplementary Table S2 show changes in incidence over time through SRRs of the most recent period (2007–2016) to the earliest period (1999–2008). Overall, most populations showed a declining trend; SRRs ranged from 0.56 [95% confidence interval (95% CI) = 0.40–0.85] among Iceland (outside the capital) males to 1.26 (95% CI = 0.73–2.79) among Greenland females. Rates among Greenland males and females, and Alaska AIAN males and females were elevated compared with regional counterparts. Rates among these populations remained stable over the period of analysis (Greenland Male SRR = 1.16, 95% CI = 0.81–1.86; Greenland Female SRR = 1.26, 95% CI = 0.73–2.79; Alaska AIAN Male SRR = 0.95, 95% CI = 0.72–1.26; Alaska AIAN Female SRR = 0.89, 95% CI = 0.63–1.27). Russian circumpolar rates were elevated compared with the national rate. Among both sexes in Northern Canada, rates were elevated compared with national counterparts. Incidence rates among both sexes in Northern Canada remained stable over the period (SRR = 0.85; 95% CI, 0.63–1.24).

Supplementary Figure. S1A and S1B present stomach cancer ASIRs by regional population, circumpolar status, and sex for the most recent ten-year period (2007–2016). Among world regions, rates for both males and females were highest in Asia, followed by the Americas and Europe.

The highest male rates were observed in Russia, with the highest in Karelia (40.8 per 100,000 PY). Outside Russia, the highest male rates were among Greenland (20.2 per 100,000 PY), followed by Alaska AIAN (18.6 per 100,000 PY), and North Jutland (Denmark; 11.5 per 100,000 PY) populations. The lowest rates were among U.S. Northeast AIAN (2.1 per 100,000 PY), U.S. South AIAN (4.0 per 100,000 PY), and Alaska White (4.4 per 100,000 PY) populations.

The highest female rates were observed in Russia, with the highest in Arkhangelsk (17.7 per 100,000 PY). Outside of Russia, the highest rates were in Alaska AIAN (ASIR = 10.3 per 100,000 PY), followed by Greenland (ASIR = 8.8 per 100,000 PY) and Turku Finland (ASIR = 5.2 per 100,000 PY) populations. The lowest female rates were among Northeast U.S. AIAN (1.2 per 100,000 PY), Alaska White (2.0 per 100,000 PY), and Midwest U.S. (2.2 per 100,000 PY) populations. Among both sexes in Canada, rates in Northern Canada were elevated compared with national counterparts (Supplementary Fig. S1B).

Stomach cancer incidence SRRs are presented in Fig. 3A and B relative to corresponding national rates (i.e., Canada, United States, Nordic countries, and Russia). In the United States, AIAN stomach cancer incidence was compared with subregional White populations (e.g., Alaska AIAN vs. Alaska White). SD choropleth maps are presented in Fig. 4A–D.

The largest male SRRs were observed among Alaska AIAN (SRR = 3.82; 95% CI, 2.71–5.37), Greenland (SRR = 2.83; 95% CI, 1.94–4.57), and the North Jutland (Denmark; SRR = 1.62; 95% CI, 1.46–1.81) populations. The largest female SRRs were observed among Alaska AIAN (SRR = 4.10; 95% CI, 2.62–6.43), Greenland (SRR = 2.28; 95% CI, 1.34–4.82), and Arkhangelsk (SRR = 1.48; 95% CI, 1.40–1.56; Fig. 3A). Among both sexes in Canada, Northern Canada had an elevated SRR of 1.54 (95% CI, 1.20–2.08; Fig. 3B).

Ten-year rolling ASMRs were plotted by regional population and sex (Fig. 5A and B). Supplementary Table S3 shows changes in mortality over time through SRRs of the most recent period (2007–2016) to the earliest period (1999–2008). Overall, most populations have shown declining trends; SRRs ranged from 0.57 (95% CI, 0.34–1.28) among Faroe Islands males to 1.16 (95% CI, 0.80–1.66) among Alaska AIAN males. Mortality rates in Russia remained the highest. Rates among males and females in Greenland, and males and females among Alaska AIAN people were elevated compared with regional counterparts. Rates among these populations remained stable over the period of analysis (Greenland Male SRR = 0.94, 95% CI = 0.59–1.82; Greenland Female SRR = 0.88, 95% CI = 0.50–2.01; Alaska AIAN Male SRR = 1.16, 95% CI = 0.80–1.66; Alaska AIAN Female SRR = 0.92, 95% CI = 0.59–1.42). Rates among both sexes in Northern Canada were also elevated compared with national comparators.

Stomach cancer MIRs were plotted by regional population and sex for the most recent 10-year period (2007–2016; Supplementary Fig. S2A and S2B). The highest MIRs was observed in Russia (male MIR = 0.86, female MIR = 0.82). Among males, this was followed by Northern Sweden (MIR = 0.83) and by Kuopio Finland (MIR = 0.81). Among females, this was followed by Zealand, Denmark (MIR = 0.81), and Northern Sweden (MIR = 0.80). In the United States, MIRs for Alaska AIAN males and females were elevated compared with other U.S. populations. Among both sexes in Canada, MIRs were elevated in the East while lowest in the North (Supplementary Fig. S2B).

This study provides a comprehensive assessment of stomach cancer incidence and mortality trends across circumpolar countries and regional subpopulations using data from population-based cancer registries. Overall, stomach cancer incidence and mortality rates declined over time in most circumpolar populations. However, among Alaska AIAN, Greenland, circumpolar Russian and Northern Canadian populations, incidence and mortality rates were elevated and remained stable. When race was considered (U.S. data only), rates were significantly elevated among Alaska AIAN compared with Alaska White populations. Patterns were not consistent among all Indigenous populations, highlighting the importance of population-specific information.

Consistent with the current findings, Canadian stomach cancer incidence declined for both sexes between 1984 and 2015 [average annual percent change (AAPC) = −1.9; ref. 8]. In the United States, incidence remained stable between 2011 and 2015 (male-AAPC = −0.6; female-AAPC = 0.0). Among Nordic countries, declining incidence among both sexes were reported between 2003–2007 for Denmark, Finland, Iceland, Norway, and Sweden (AAPC range, −2.8 to −5.1; ref. 47). Stomach cancer mortality rates in Canada, United States, and Nordic Countries showed strong declines during these periods, respectively (8, 9, 48). Among 38 countries globally, Russia had the second highest age-standardized incidence rates behind Japan (47). A significant decline was reported between 1993 and 2007 of −2.8% (47). Among population groups, sex-specific trends in incidence and mortality were similar, yet males consistently had higher rates than females. While this observation is consistent with the literature, sex-specific differences are not well understood (2). Declining incidence and mortality rates are attributed to advancements in sanitation, availability of fresh foods, reduced use of preservatives like salt, declining smoking prevalence, and increased recognition and treatment of H. pylori (48–50).

Stomach cancer incidence and mortality rates were reported to be elevated among Alaska AIAN people relative to Alaska and U.S. White people. Stomach cancer incidence rates from 2005 to 2016 among non-Hispanic Alaska AIAN people were 4.23 times greater than non-Hispanic Alaska White people (males-RR = 3.93; females-RR = 5.39; ref. 13). Compared with Alaska non-Hispanic White people, Alaska Native people from 2006 to 2014 had higher stomach cancer incidence and were more likely to be diagnosed younger and develop non-cardia stomach cancer (51). White and colleagues also reported higher mortality-incidence ratios among non-Hispanic AIAN people compared with non-Hispanic U.S. White people suggesting disparities in diagnosis and treatment (11).

This study shows elevated stomach cancer incidence and mortality rates in northern Canada. Stomach cancer mortality in the Yukon Territory was 2.6 times greater than expected, relative to national rates (15). However, incidence rates were not different from national rates (14, 52). An important limitation in Yukon is the inability to report on Indigenous specific rates. In the Northwest Territories, Colqhoun and colleagues found elevated rates of noncardia stomach cancer among Indigenous people compared with national rates [male standardized incidence ratio (SIR) = 2.7; female-SIR = 3.1] but not for non-Indigenous people (male-SIR = 0.94; female-SIR = 0.62; ref. 14).

Similar to this study, Yousaf and colleagues reported elevated stomach cancer incidence and mortality in Greenland between 1984 and 2014 compared with Nordic countries (16). This pattern in Greenland was similar to those reported among other circumpolar Inuit populations (53). There are few studies comparing stomach cancer trends regionally in Russia. International partnerships between Norway and northwestern Russian cancer registries have supported research activities (54). Similar to these findings, stomach cancer incidence in Arkhangelsk was reported to be elevated compared with Russia overall between 1993 and 2001 (54).

In a Norwegian cohort study, stomach cancer incidence among Sami people between 1970 and 1997 was not significantly different compared with a regional reference population (male-SIR = 0.91, female-SIR = 1.06; ref. 22). In Finland, Sami people overall had lower SIRs of stomach cancer relative to non-Sami people from 1979 to 1998, with the exception of Skolts people (SIR = 3.8; ref. 55). This was attributed to declines from traditional ways of life and socioeconomic status after emigration from Russia (55). In Sweden, Northern Sami people had similar cancer rates to the Northern general population between 1961–1997; only stomach cancer was found to be elevated (55, 56). Elevated risk was attributed to a diet high in smoked and salted foods and low in fruits and vegetables (57).

H. pylori's attributable risk for stomach cancer globally, specifically noncardia stomach carcinoma, is 89% (95% CI, 79%–94%; refs. 5, 58). H. pylori was the most important infectious cause of cancer in countries with high and very high human development index scores (HDI; ref. 5). It is estimated to colonize the stomach mucosa of nearly half the human population (59). Field studies in the Canadian Arctic reported high rates of H. pylori among Indigenous communities compared with national counterparts (17, 60–65). Prevalence among Indigenous communities in Yukon and NWT ranged from 58% to 69% (60). Prevalence Canada-wide was estimated to be 30% among dyspeptic patients (66). In Alaska, seroprevalence for H. pylori among AIAN people was 63% compared with 24% among non-Indigenous Alaskans (67). Nation-wide, seroprevalence was 27% (68). Other studies among Alaska Native people have reported seroprevalence of 75%–80% (69, 70). Alaska Native people also have higher rates of H. pylori reinfection after successful eradication (22% at two years) relative to other U.S. populations (<5% at two years; ref. 67). Furthermore, a high proportion of H. pylori isolates among Alaska Natives demonstrate resistance to common antimicrobials (71). High rates of treatment failure have been documented (72–74). The U.S. CDC's Arctic Investigations Program and the Alaska Native Tribal Health Consortium are supporting the development of pilot studies for early screening of stomach cancer among Alaska Native people (64).

Seroprevalence for H. pylori was significantly elevated among Inuit in Greenland (46.5%) compared with Caucasian people from Denmark (26.5%; refs. 75). Another study reported seroprevalence of 58% among Inuit adults in Greenland (76). H. pylori prevalence for other Nordic countries were reported to be lower: Iceland (33%, 1975–1997; ref. 77), Sweden (18.0%, 1995), and Finland (19.0%, 2001; ref. 78). In Finland, strong declines were reported from 1983 (30.1%) to 1995 (13.1%). Declines were less prominent in northern Finland where seroprevalence was significantly elevated (21.6%, 1995) compared with national estimates (79). In Russia, H. pylori prevalence among an Indigenous circumpolar population (Chukotka males) was 77.0% (21, 80).

High salt intake and smoking are associated with an increased risk of developing stomach cancer (81). Among a European population, smoking accounted for 17.6% of stomach cancers (82). High meat intake was associated with an increased risk of noncardia cancer, especially in H. pylori antibody–positive subjects (83). Fruit and vegetable intake were protective of stomach cancer, irrespective of H. pylori status (84). Another study reported a protective effect depending on both H. pylori status and virulence factors (85).

Some elements of traditional foods, and changes in the accessibility of traditional foods, may influence stomach cancer incidence among northern and Indigenous circumpolar populations. Nilsson and colleagues reported high intakes of red meat and low intakes vegetables and fruit among the traditional Sami diet (86). Bjerregaard and colleagues reported declines in traditional food systems among Inuit populations as a result of environmental, socioeconomic, and political factors woven into the legacy of colonialism (7, 87). In the United States, there was a lower proportion of fruit and vegetable intake among Alaska non-Hispanic AIAN females (21.5%) than U.S. non-Hispanic White females (28.4%), but not males (88). Circumpolar populations are challenged by remote location, elevated food costs, and the impact of climate change on use of traditional foods (89–91).

Smoking prevalence was elevated among populations with high stomach cancer incidence. The prevalence of current smokers among Alaska non-Hispanic AIAN (males = 41.4%; females = 36.8%) was high compared with U.S. non-Hispanic White people (males = 21.6%; females = 20.2%; ref. 88). Smoking prevalence was 20.2% and 35.0% in the Yukon and Northwest Territories (92), respectively, and 63% among Inuit in Nunavut (93). Among southern Canadian provinces, it was 15.8% (94). Among Nordic countries, smoking prevalence declined over time but with geographic variation. The proportion of adult daily or occasional smokers was 14% in Sweden, followed by Iceland (15%), Norway (19%), Denmark (22%), Finland (23%), and the Faroe Islands (27%; ref.95). In Greenland, it was 60% (2014; ref. 95). In 2016, smoking prevalence among Russian adults was 30.7%, but has declined since 2009 (96).

This study has major strengths. We report on cancer incidence and mortality using data from population-based cancer registries across eight nations. Nearly 20 years of data enabled reporting among regional and ethnic subpopulations with small populations. In the United States, AIAN race was examined, highlighting the importance of population and region-specific trends. The study has a number of limitations. This study does not distinguish between cardia and noncardia stomach cancers, which have etiologic differences. This level of detail in the data was not available. Indigenous status was not available from non-U.S. cancer registries. Among U.S. data, where Indigenous status was available, numerator–denominator bias may be present (42). Many northern and Indigenous populations were typically small in size and case counts. We chose large geographic regions and examined 10-year rolling rates to assess general trends. Rolling trends are not independent and both ten-year and large geographic aggregations mask granular trends. Canadian incidence data were available as randomly rounded counts (to the nearest 0, 5, or 10) at annual, sex, and regional levels, contributing to noise in ASR estimates, particularly among smaller populations.

Stomach cancer incidence and mortality rates have declined overall among circumpolar nations. However, many northern and Indigenous populations experience elevated and stable stomach cancer incidence and mortality rates while declines were observed among regional counterparts. The main risk factor, H. pylori, is elevated in many northern regions and Indigenous populations. Among Alaska Native people, antimicrobial resistance, increased pathogenicity and high re-infection rates have been reported. There is a need to address disparities in stomach cancer incidence and mortality experienced by many circumpolar populations. Furthermore, there is an opportunity to coordinate cancer prevention and control strategies across the circumpolar countries experiencing similar disparities.

J. Simkin reports grants from Canadian Institutes of Health Research during the conduct of the study. No disclosures were reported by the other authors.

The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the U.S. Centers for Disease Control and Prevention and other affiliated organizations. The Canadian Institutes of Health Research had no involvement in development of this manuscript.

J. Simkin: Conceptualization, resources, data curation, software, formal analysis, supervision, funding acquisition, validation, investigation, visualization, methodology, writing–original draft, project administration, writing–review and editing. S.H. Nash: Conceptualization, data curation, formal analysis, investigation, visualization, methodology, writing–original draft, project administration, writing–review and editing. A. Barchuk: Data curation, software, formal analysis, validation, investigation, visualization, methodology, writing–review and editing. D.K. O'Brien: Conceptualization, data curation, formal analysis, investigation, visualization, methodology, writing–review and editing. A.C. Erickson: Formal analysis, supervision, investigation, visualization, methodology, writing–review and editing. B. Hanley: Conceptualization, resources, data curation, supervision, investigation, methodology, writing–original draft, writing–review and editing. H. Hannah: Conceptualization, data curation, investigation, visualization, methodology, writing–review and editing. A. Corriveau: Conceptualization, data curation, investigation, visualization, methodology, writing–original draft, writing–review and editing. I.K. Larsen: Data curation, formal analysis, investigation, visualization, methodology, writing–original draft, writing–review and editing. C.W. Skovlund: Data curation, formal analysis, investigation, visualization, methodology, writing–review and editing. S. Larønningen: Data curation, formal analysis, investigation, visualization, methodology, writing–review and editing. T.J.B. Dummer: Data curation, formal analysis, supervision, investigation, visualization, methodology, writing–review and editing. M.G. Bruce: Conceptualization, data curation, formal analysis, supervision, investigation, visualization, methodology, writing–original draft, writing–review and editing. G. Ogilvie: Conceptualization, resources, data curation, supervision, funding acquisition, validation, investigation, visualization, methodology, writing–original draft, project administration, writing–review and editing.

The authors would like to acknowledge the Canadian Institutes of Health Research for their support through the Canada Graduates Scholarships Doctoral Award. J. Simkin is a recipient of this award. The scholarship provides financial support for students in doctoral studies.