The study, published in the journal Cancer Causes & Control, drew on records from the North Carolina Central Cancer Registry covering the years 2003 through 2021. The investigators constructed two analytic cohorts: a diagnosis cohort comprising 111 non-Hispanic American Indian and Alaska Native patients and 7,685 non-Hispanic white patients, and a treatment cohort of 97 American Indian and Alaska Native patients and 6,040 white patients for whom treatment information was available. By restricting the analysis to North Carolina and comparing the two groups directly, the team aimed to provide the first baseline assessment of the gastric cancer burden borne by American Indian communities in the state, a population that has historically been undercounted and understudied in cancer surveillance research.

The demographic and clinical profile of gastric cancer differed markedly between the two groups. American Indian and Alaska Native patients were diagnosed at a median age of 65 years compared with 68 years for white patients, a difference that was statistically significant. The anatomical distribution of their tumors also diverged: 80 percent of American Indian and Alaska Native patients had non-cardia gastric cancer, tumors arising in the lower portions of the stomach, whereas the corresponding figure among white patients was 62 percent. This distinction matters clinically because cardia and non-cardia gastric cancers have different risk factor profiles, different patterns of occurrence across populations, and different associations with infection by the bacterium Helicobacter pylori, a well-established cause of gastric carcinoma.

Stage at diagnosis also differed, with 36 percent of American Indian and Alaska Native patients diagnosed at a later stage compared with 32 percent of white patients, a modest but statistically significant difference. The two groups differed just as sharply in where they lived. Fully 76 percent of American Indian and Alaska Native patients resided in areas with low residential population density, compared with only 26 percent of white patients. This rural concentration is more than a descriptive footnote; rural residence is associated with longer travel distances to specialized cancer centers, reduced access to gastroenterologists and oncologists, and documented delays in cancer diagnosis and treatment across many malignancies. Any explanation of the treatment gaps observed in this study must contend with the geography of the affected communities.

To quantify the treatment disparity, the researchers analyzed the risk of receiving no documented treatment at all and the timing of the first treatment after diagnosis. Using modified Poisson regression, a statistical technique well suited to modeling common binary outcomes while estimating risk ratios directly, they estimated the multivariable-adjusted association between race and failure to initiate treatment. The adjusted risk ratio was 1.13, with a 95 percent confidence interval spanning 0.87 to 1.47 and a p-value of 0.34. In other words, American Indian and Alaska Native patients had a point estimate suggesting a thirteen percent higher risk of receiving no treatment, but the wide confidence interval means the data cannot rule out effects ranging from a modest reduction to a nearly fifty percent increase in risk. The authors were careful to present this result as inconclusive rather than as evidence of no difference.

The timing analysis told a more consistent story. The team estimated race-specific cumulative incidence functions for treatment initiation, a method that accounts for the possibility that some patients die before starting treatment, and refined these estimates using inverse probability weighting to adjust for key covariates such as age, stage, and socioeconomic characteristics of the patients’ residential areas. Confidence intervals were obtained through bootstrapping, a resampling approach that makes minimal assumptions about the underlying distributions. The cumulative incidence of treatment initiation was consistently lower for American Indian and Alaska Native patients throughout follow-up, and at thirty days after diagnosis the difference was statistically significant, with a cumulative incidence difference of minus 0.09 and a 95 percent confidence interval of minus 0.17 to minus 0.01. Nine percentage points fewer American Indian and Alaska Native patients had begun treatment within the first month.

Why does a thirty-day delay matter? In gastric cancer, as in many solid tumors, time to first treatment is a widely used quality-of-care indicator, and delays are associated with disease progression, reduced eligibility for curative surgery, and worse survival. A nine-percentage-point gap in the first month, sustained across the first year after diagnosis, suggests a systematic difference in how quickly patients move from diagnosis to oncologic care, whether because of barriers in referral pathways, insurance and authorization hurdles, transportation and lodging challenges in rural areas, patient-provider communication, or differences in tumor biology and comorbid illness that complicate treatment planning. The study was not designed to isolate which of these mechanisms dominates, but the consistency of the timing gap, in contrast to the imprecise estimate for receiving no treatment at all, points toward delays rather than outright withholding of care as the central disparity.

The findings fit into a broader national picture. Previous research has documented elevated gastric cancer incidence and mortality among American Indian and Alaska Native populations in the United States, with particularly high rates in Alaska and certain regions of the country, and prior work has linked these patterns to higher prevalence of Helicobacter pylori infection and its virulent strains in some Native communities. The North Carolina study extends this literature by focusing on a state with a large, diverse Native population that includes both federally and non-federally recognized tribes, and by adding the dimension of treatment timeliness, which had been examined nationally but not previously at the state level for this population. The authors also situate the work within a series of recent North Carolina analyses of cancer burden and end-of-life care quality among American Indian patients conducted with the Cancer Information and Population Health Resource at the UNC Lineberger Comprehensive Cancer Center.

The researchers acknowledge important limitations inherent to registry-based studies of Native populations. Racial misclassification is a persistent problem in state cancer data; earlier work in North Carolina has shown that American Indian race is sometimes misrecorded among members of non-federally recognized tribes, which could bias incidence and outcome estimates in either direction. Registry treatment information may also be incomplete, particularly for care delivered outside reporting facilities, and the modest number of American Indian and Alaska Native patients, 111 in the diagnosis cohort, limits statistical power and explains the wide confidence interval around the risk ratio for no treatment. The investigators addressed the treatment-data concern by noting prior validation work on registry-based treatment information and by using documented receipt of treatment as the outcome, while the small-sample problem was handled through robust variance estimation and bootstrapped intervals rather than ignored.

For public health practitioners and oncologists in North Carolina and beyond, the study delivers a clear message: gastric cancer in American Indian and Alaska Native communities presents differently, is caught later, and reaches treatment more slowly than in the white population, and these differences are measurable with the surveillance systems already in place. The authors frame their results as a baseline against which future interventions can be judged, whether those interventions target earlier detection of non-cardia tumors in younger Native patients, streamline the diagnostic-to-treatment pathway in rural counties, or expand culturally grounded patient navigation. Given that gastric cancer is often preventable through detection and eradication of Helicobacter pylori and that survival depends heavily on stage at diagnosis, closing the thirty-day treatment gap identified here could translate into concrete survival gains for a population that has carried a disproportionate share of this disease for far too long.

Subject of Research: Racial disparities in gastric cancer diagnosis and time-to-first-treatment between non-Hispanic American Indian Alaska Native and white patients in North Carolina

Article Title: Characterizing gastric cancer and time-to-first treatment among non-Hispanic American Indian Alaska Native and white patients in North Carolina

Article References: Uhrin, M. T., Jackson, B. E., Baggett, C. D., Spees, L. P., Begay, J. A., Epplein, M., Wheeler, S. B., Bell, R. A., & Emerson, M. A. (2026). Characterizing gastric cancer and time-to-first treatment among non-Hispanic American Indian Alaska Native and white patients in North Carolina. Cancer Causes & Control, 37(10), Article 173. https://doi.org/10.1007/s10552-026-02254-w

Image Credits: AI Generated

DOI: 10.1007/s10552-026-02254-w

Keywords: gastric cancer, American Indian, Alaska Native, health disparity, time to treatment, North Carolina, cancer registry, Helicobacter pylori, non-cardia gastric cancer, rural health, cancer epidemiology, Cancer Causes & Control

The study, published in the journal Cancer Causes & Control, drew on the Multiethnic Cohort Study, a prospective population-based investigation that enrolled more than 215,000 residents of Hawaii and California between 1993 and 1996. Participants aged 45 to 75 completed detailed baseline questionnaires covering diet, medications, occupation, physical activity, family history of cancer, and immigration history. The research team, led by Haejin In of the Rutgers Cancer Institute together with Meira Epplein of Duke University, restricted their analysis to individuals who identified as Japanese or non-Hispanic White, ultimately following 94,232 participants for a median of just over 20 years. During that time, 716 primary gastric cancer cases were identified through statewide SEER cancer registries in Hawaii and California.

The central innovation of the study was its use of generational immigration status, a classification built from the birthplaces of the participants and their parents. Japanese descendants were divided into four groups: those born in Japan themselves, US-born individuals with both parents born in Japan, US-born individuals with one parent born in Japan, and US-born individuals whose parents were both born in the United States. Non-Hispanic White participants served as the reference group. The researchers then used Cox proportional hazards models, with age as the time scale, to estimate how gastric cancer risk varied across these groups while adjusting for a wide range of demographic, dietary, and lifestyle variables, including education, body mass index, smoking, alcohol consumption, fruit and sodium intake, diabetes history, and family history of the disease.

The results were unambiguous. Japan-born participants had a 4.62-fold higher hazard of developing gastric cancer compared with non-Hispanic Whites. Among US-born participants, the risk declined in a clear gradient: those with both parents born in Japan had a 3.66-fold higher hazard, those with one Japan-born parent had a 3.39-fold higher hazard, and those whose parents were both born in the United States had a 2.57-fold higher hazard. The trend across generations was highly statistically significant, with a p-value for trend below 0.0001. When the two second-generation groups were combined, their pooled risk was 3.59 times that of non-Hispanic Whites, confirming a progressive attenuation of risk across generations rather than a sharp drop confined to the transition from the first to the second generation.

Perhaps the most striking finding emerged when the researchers broke the results down by anatomical subsite. The generational association was driven almost entirely by non-cardia gastric cancer, the type that arises in the lower portions of the stomach and is most strongly linked to chronic infection with the bacterium Helicobacter pylori. First-generation Japanese descendants had a nearly six-fold increased risk of non-cardia cancer compared with non-Hispanic Whites, second-generation descendants a 4.5-fold increased risk, and third-generation descendants roughly a three-fold increased risk. When the analysis was restricted to precisely defined non-cardia subsites, the associations grew even stronger, with the first-generation hazard ratio reaching 7.13. In contrast, the associations for cardia cancer, the type arising near the junction with the esophagus, were weaker and showed no statistically significant linear trend across generations.

What could explain such a persistent, generational gradient? The leading hypothesis centers on Helicobacter pylori, the bacterium considered one of the major drivers of gastric cancer development. People who migrate from countries where H. pylori is highly prevalent are more likely to have acquired the infection during childhood, a critical window when chronic gastric inflammation can become established and shape long-term susceptibility to carcinogenesis. Persistent childhood infection is also associated with more virulent bacterial strains, such as those carrying the cagA and vacAs1m1 genes, which may disrupt early-life microbiota and immune regulation. Although H. pylori prevalence is known to decline across generations within immigrant families, the fact that third-generation Japanese descendants still face nearly triple the risk of non-Hispanic Whites suggests the bacterium alone cannot account for the full picture.

The authors point to a constellation of additional mechanisms that may be transmitted across generations or interact with the post-migration environment. Dietary acculturation is one candidate: first-generation immigrants in the cohort consumed the most sodium, a known risk factor for non-cardia gastric cancer, with intake declining in each subsequent generation, while body mass index rose across generations. Prior research has shown that a Westernized diet and lifestyle alter the gut microbiome, causing US-associated microbial communities to replace native Asian ones, with effects that intensify the longer a person lives in the United States. Studies of Japanese descendants have also documented a preference for Japanese food in the second generation giving way to Western foods in the third, alongside microbiome alterations linked to insulin resistance. Epigenetic programming may play a role as well; a cross-sectional study of Italian migrants found differences in DNA methylation compared with non-migrants even after adjusting for diet and lifestyle. Genetic variation adds yet another layer, with certain polymorphisms in inflammatory pathway genes, such as interleukin-1, reported among Japanese individuals to modify gastric cancer risk independently of H. pylori infection or smoking.

Notably, the researchers found no evidence that established risk factors, including family history of gastric cancer, education, body mass index, smoking status, and sodium intake, modified the association between generational status and cancer risk. This suggests that the generational gradient reflects distinct environmental, biological, or early-life influences rather than simple differences in these conventional exposures. The findings echo earlier work, including a landmark study by Kamineni and colleagues showing that first-generation Japanese immigrants to the United States had higher gastric cancer incidence than US Whites but lower rates than people in Japan, and a Hawaiian study by Kolonel and colleagues finding higher incidence among Japan-born than US-born Japanese residents. The new study extends this evidence with individual-level exposure data and more than two decades of prospective follow-up, advantages that registry-based studies could not provide.

The clinical implications are significant. Because the United States does not operate population-wide gastric cancer screening programs, unlike Japan and South Korea, identifying which groups stand to benefit most is essential. The marked differences in risk across immigrant generations, even within a single self-identified ethnic group, suggest that generational status could serve as a practical marker for risk-stratified screening. Prior studies have demonstrated the cost-effectiveness of gastric cancer screening among high-risk US groups, including Asian Americans undergoing upper endoscopy, opportunistic endoscopic examination during routine colonoscopy, and non-invasive biomarker approaches such as serum pepsinogen testing. Concentrating surveillance resources on the most at-risk generations could improve both the effectiveness and the accessibility of gastric cancer prevention for minority populations.

The study has limitations worth noting. Self-reported race and ethnicity may not perfectly reflect genetic ancestry, information on H. pylori infection itself was not available, and the cohort was drawn from Hawaii and California, regions with long-established Japanese American communities whose migration and acculturation patterns may differ from those of Japanese descendants elsewhere in the country. The authors call for replication in geographically diverse cohorts with detailed data on age at migration and duration of US residence. Still, the core message stands: the legacy of where a family came from, and when, is written into cancer risk for at least three generations. Understanding these transgenerational determinants, the authors argue, could reshape how the United States screens, detects, and prevents one of the world’s deadliest cancers.

Subject of Research: Generational immigration status and gastric cancer incidence among Japanese descendants in the Multiethnic Cohort Study

Article Title: Generational immigration status and gastric cancer incidence among Japanese descendants: an analysis of the Multiethnic Cohort (MEC) Study

Article References: In, H., De la Torre-Cisneros, K., Adams, A., Chen, C., Rana, B., Wilkens, L., & Epplein, M. (2026). Generational immigration status and gastric cancer incidence among Japanese descendants: an analysis of the Multiethnic Cohort (MEC) Study. Cancer Causes & Control, 37(10), Article 168. https://doi.org/10.1007/s10552-026-02250-0

Image Credits: AI Generated

DOI: 10.1007/s10552-026-02250-0

Keywords: gastric cancer, Japanese descendants, immigration generation, Multiethnic Cohort Study, Helicobacter pylori, non-cardia gastric cancer, health disparities, cancer screening, epidemiology, dietary acculturation, Cox proportional hazards, cancer risk