Gastric cancer (GC) is one of the most frequent cause of tumors in the digestive system, with an estimated 26,560 new cases per year in the United States. It also remains the leading cause of cancer-related deaths (1). Gastric adenocarcinoma (GAC) is the most common type of gastric malignancy, accounting for ~95% of all types of GC (2). With advancements in therapeutic modalities, an improvement in GC patients' survival rate has been observed, whereas the 5-year overall survival (OS) rate is generally below 30% and the median relative survival rate is just 16 months (3). Moreover, prognoses for patients are highly dependent on the stage at diagnosis. The 5-year OS for those with distant metastases is <5% (3), and chemotherapy remains the preferred choice of treatment for the patients with an advanced GC (4). As a multifactorial disease, the environmental, demographic, and the genetic factors play pivotal roles in the etiology and lead to survival disparities in patients with GC (5). Given the very poor prognosis for patients with GC, the discovery of any factor that predicts better survival outcomes could be highly beneficial.

Socioeconomic status (SES) factors, including insurance status, marital status, income level, and education level, have been reported to influence the morbidity risk, treatment approaches, and long-term prognoses for patients with GC (6–15). Increased survival rates for patients with GC have been observed over the past few decades with a widening SES gap (11). Lower SES is linked to inferior survival rates (7, 11). In addition, patients whose SES is low have a lower probability of curative treatment allocations for gastrointestinal cancers, resulting in dismal prognoses (14). Besides, an adverse marital status (divorced or widowed), living alone, low education level, and low income increase the risks of all GC subtypes (8). A case–control study suggests that the education level could be a reliable and ideal single indicator to measure GC risk among several SES variables (15). Nevertheless, the impact of education level on the GC survival rate remains poorly understood.

Educational attainment is recognized as a crucial social determinant of diseases; it influences health through mechanisms such as biological aging, cognitive ability, and health behaviors (16). Education level has been demonstrated to impact treatment and prognoses in anal cancer, sinonasal cancer, and multiple myeloma (17–19). A nationwide cohort study in Sweden indicated that a high education level was associated with a greater likelihood of improved survival rates and curative treatment in 4,112 patients diagnosed with gastroesophageal cancer (10). Another investigation of 4,709 patients with stomach cancer in Sweden did not show a significant influence of education level on cancer survival rates (20). Considering the lack of such studies in the United States, as well as differences in education systems and patient characteristics between the two countries, we utilized the Surveillance, Epidemiology, and End Results (SEER) database to conduct a large-scale retrospective study in the United States. We investigated the effects of education level and other socioeconomic factors (e.g., income level, unemployment rate, insurance status, marital status) on the treatment receipt and clinical outcomes of patients with GAC.

Of note, SES proved to play a vital role in the pathogenesis of the disease and survival rate of patients with GC (6, 7, 11), yet there remains a paucity of evidence on the prognostic effects resulting from education level. It is necessary to elaborate on this issue with a large population-based study. Through SEER data, we clarified that low education level was significantly linked to diminished survival rates in patients with GAC, serving as an independent and robust predictor. This view was strengthened by evidence from the subgroup analysis. Moreover, a higher risk for receiving no treatment was observed among patients in counties with low education levels, which explained their poor prognoses to some extent.

Our results confirm that a high level of education confers survival advantages, regardless of other variables. This finding is consistent with that of a previous study on gastroesophageal tumors (10). By contrast, our study included more recently diagnosed patients, larger sample sizes, and a longer follow-up period. The classifications for educational status were determined rationally by referring to a specialized index of educational degrees. Two earlier studies based on the European population also reported that a higher education level was a favorable prognostic factor in patients with GC (21, 22), which further supports our conclusion. However, these two studies only assessed the impact of simple SES on the survival of patients with GC; clinical factors were not considered. We included detailed clinical variables and confirmed the importance of education level after adjusting for covariates. Moreover, we conducted comprehensive subgroup analyses to fully describe that a low education level carries a higher risk for both OS and CSS in almost every subgroup, highlighting its broad applicability as a prognostic predictor. Nevertheless, we noted that the effect of education category was not so significant for NHB and patients with Grade IV tumor, most likely because of the small sample size of the NHB group. For the latter, a higher tumor grade was positively correlated with the development of a distant metastasis. leading to very poor survival rates for patients with GC (23). This finding could potentially attenuate the effects of education.

A prognosis is largely dependent on treatment modalities and types. As expected, in this study, patients undergoing a combination of surgical resection and chemotherapy experienced the best survival benefits; specifically, gastrectomy performed after chemotherapy led to superior outcomes (24, 25). The survival trends also persisted in stage IV patients, for whom prognoses were quite dismal (as illustrated by the Kaplan–Meier curves). For this population, palliative chemotherapy with supportive care remains the main treatment modality (4, 26). We performed a logistic regression analysis to validate the role of education in the use of cancer treatments. Here, we report for the first time that a low education level is strongly associated with a lack of therapy in patients with stage IV GC, and this finding complements the two other studies on non-advanced or regional GC (14, 27). However, radiotherapy was not associated with significant survival differences, which is likely due to the low sensitivity of GAC to radiotherapy. Currently, the role of radiotherapy in adjuvant treatment or palliative treatment for GC is less certain (28, 29).

Similar findings have also been reported for other tumor types (10, 17–19), indicating that education disparities are imperative public health concerns. Thus, we were interested in the underlying effects of individual education levels for patients with cancer. First, patients with high education levels tend to be in high SES categories, with easier access to health care and greater financial resources, which typically guarantee better health outcomes. Evidence also supports financial income as positively related to health status (30). Second, high educational attainment has positive impacts on vigorous physical exercise regimens and negative impacts on smoking, poor diet, sedentary habits, and other unhealthy behaviors (31). Convincing data show that appropriate diet, physical activities, and normal BMI have survival benefits for cancers (32), as they are associated with such biological hallmarks as immune responses, epigenetic regulation, and rhythm disorders (33). Third, highly educated patients have higher levels of health awareness (i.e., understanding medical information and receiving effective interventions) (34). Fourth, from a psychological perspective, the patients with higher education levels are less likely to become depressed or low-spirited (35). Depression or psychosocial stressors can drive tumor progression and cause worse outcomes through a large number of biobehavioral pathways (36). Fifth, employment rates and income levels are both higher among the better educated patients, which may facilitate their access to advanced treatment regimens with superior continuity and completion. However, the inadequacy is that the examined variable is not the real measure of individual education levels. Our explanations are just based on the putative correlation between county-level education and individual-level education. In county-level terms, counties characterized by high SES have greater medical resources and services compared to those characterized by low SES. Counties with sufficient resources also have greater financial support, more Medicaid funding and programs, and a higher prevalence of academic centers, clinical trials, and collaborations with pharmaceutical companies. Moreover, counties known for high SES have populations that are wealthier, more educated, and more likely to be employed and insured, and these differences in the composition of patient demographics may contribute to the positive effects on survival.

In addition to education level, we identified other demographic factors associated with the treatment and survival for the patients with GAC. Married patients had the lowest rate for no treatment and the highest acceptance rate of chemotherapy compared with the three other unmarried groups. A good marriage may provide adequate economic resources and social support as the basis for treatment regimens. On the contrary, widowed patients suffered the worst survival rates, possibly because they were less likely to receive treatment and had less social support, higher levels of loneliness, and an inferior insurance status. We also point out that uninsured or Medicaid patients had a significantly higher risk of no treatment. One reasonable explanation for this finding is that an uninsured or Medicaid status is more likely to be linked to poverty, low education levels, and other unfavorable SES factors. Interestingly, those with high income levels tended be less vulnerable to low education levels, according to the forest plots. This means that the adverse effect of a low level of education can possibly be compensated by increasing an individual's revenue. Notably, the beneficial effects of a high education level were the most obvious in the early stages of tumor development, including localized stage, AJCC stage I, and Grade I tumors, and non-metastatic status. The potential reasons for the favorable prognoses of highly educated individuals are advanced health consciousness, earlier diagnosis, and more effective interventions.

The present study has several limitations. First, sociodemographic variables provided by the SEER database were at the county-level rather than the individual level. The principal conclusions were dependent on an investigation at the community level; personal information was lacking. Nevertheless, this is still a reliable measure with practical implications for assessing SES, which has always been widely applied in SEER-based socioeconomic studies. Second, our results only reflect part of the affected population in the United States, and it remains uncertain whether these findings can be applied to other regions of the world. Lastly, we have provided comprehensive evidence of associations between education level and GC but no formal proof of causality. Further statistical methods need to be employed to evaluate casual effects.

While patient knowledge and education levels will remain relatively unchanged among older adults, the adverse sociodemographic status attributed to education levels cannot be ignored. More effective interventions are warranted to mitigate the unfavorable effects from low education levels and SES. Clinicians should enhance health education for patients to promote their health perceptions and behaviors. Governments and medical institutions are also expected to provide equal access to health care resources and services for those vulnerable groups. Income level, insurance status, marital status, and other socioeconomic elements are also involved in multifactor interactions of the disease treatment process. Long-term tracking in the dynamic changes of these factors will be informative for explaining the mechanisms.

To conclude, the education level is sufficiently established as an independent predictor for survival differences in patients with GAC. Our study indicates that the higher education levels may offer greater survival benefits and increase chemotherapy receipt. With predictions based on the education levels, designing personalized and suitable treatment plans in clinical practice is a promising approach.

The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding author/s.

All authors made a significant contribution to the work reported, whether in the conception, study design, execution, acquisition of data, analysis, and interpretation, or in all these areas. Additionally, all authors took part in drafting, revising, and reviewing the article, giving final approval to the version to be published, agreeing on the journal to which the article has been submitted, and remaining accountable for all aspects of the work.

This work was supported by the grant from the Medical Science and Technology Development Foundation, Nanjing Department of Health (YKK20083).

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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