1 INTRODUCTION

Cancer is the leading cause of death among Latinos, surpassing heart disease, the primary cause of mortality among non-Hispanic Whites (NHWs).^{1, 2} Latinos comprise 18.5% of the US population³ and are projected to reach 28.6% by 2060.⁴ Latinos comprise 39.7% of all Texans, and Texas Latinos account for about 17% of the entire US Latino population. South Texas (STX), a 38-county region encompassing San Antonio south to the Lower Rio Grande Valley along the Texas–Mexico border, is nearly 70% Latino.⁵

Compared to NHWs, Latinos have higher risk of developing multiple cancers, including gastric cancer (GC).⁶ GC is the third leading cause of cancer death worldwide⁷ and is the sixth- and eighth leading cause for Texas men and women, respectively, in 2012–2016.¹ Mortality rates from 2012 to 2016 were twice as high for Latino than NHW men and 2.4 times higher for Latino than NHW women. Gastric adenocarcinomas (GCAs) account for approximately 90% of all GCs and are the focus of this study.

GC incidence has been increasing in persons aged <50 years and Latino women.^{7, 8} In 2018, the probability of developing invasive GC at any age was twice as high in Latino versus NHW men (1.6 vs. 0.8), and three times higher in Latino versus NHW women (1.2 vs. 0.4).¹ Moreover, Latinos are diagnosed at younger ages and more advanced stages compared to other ethnic groups.^{1, 9, 10}

Latinos are disproportionately vulnerable to cancer due to increased poverty, decreased education, low or no insurance, and high prevalence of risk factors like obesity¹ and heavy alcohol consumption.⁶ About 22% of STX residents on average had an income below 150% of the federal poverty line in 2018 (range 7.3%–35%), compared with the US national average of 12%.¹¹ Our previously published review of health conditions in STX versus Texas and the US examined data on health insurance, obesity, alcohol use, and smoking.¹² For the period 2007–2010, an estimated 30% of STX residents were uninsured compared to 23% in the rest of Texas and 15% nationwide. Latinos had the highest uninsured rate (40%). STX also had the highest percentage of obese adults (32.7% vs. 29.1% in the rest of Texas and 27% in the United States). STX Latinos were more obese (37.9%) than NHWs (24.6%). STX diabetes rates were likewise higher than the rest of Texas and national estimates (11.6% vs. 9.3% and 8.9%, respectively), with Latinos again accounting for larger proportions of diabetics. Although alcohol use and smoking were similar in all three regions, binge drinking rates were higher in STX (17.4%) than the rest of Texas (14.5%) and the nation (15.1%).

The social deprivation index (SDI) is a composite measure of county-level deprivation based on seven American Community Survey (ACS) measures for income, education, employment, housing, household characteristics, and transportation.¹³ The SDI has been previously used to quantify the socioeconomic variation in health outcomes, including diabetes prevalence, odds of received colon and cervical cancer screening, and surgical treatment of head and neck cancers.^{14, 15}

Previous studies have reported mixed results on ethnic disparities in GCA trends. Two studies using Surveillance, Epidemiology, and End Results (SEER) and National Program of Cancer Registries data from 1992 to 1998 and 1976 to 2007 found that Caucasians had a 1.7 times higher GCA incidence rate and increased gastric body GCs, respectively, compared to White Latinos.^{16, 17} In contrast, studies in Southern California and Texas (using Texas Cancer Registry data) found increased odds of GC in racial/ethnic minorities and a higher GCA incidence in Latinos, respectively (with a 29% excess risk in El Paso County), compared to the NHW population.^{18, 19} Short time frame, lack of GCA anatomic site data, and failure to compare Texas data with national trends were limitations of these studies. Finally, Balakrishnan and colleagues’ retrospective cohort study of 299 non-cardia GC cases between 2005 and 2015 in the Harris County, Texas public medical system found increasing incidence among Hispanics/Latinos but not NHWs or Blacks.²⁰

The current study aimed to compare the rates and late-stage diagnosis for all primary GCA in Latinos and NHWs from 2004 to 2016 in the United States, Texas, and STX using multilevel modeling. The goal was to elucidate existing differences and the influence of specific risk factors in order to facilitate novel interventions aimed at reducing gastric adenocarcinoma incidence in specific high-risk, diverse populations.

2 METHODS

3 RESULTS

4 DISCUSSION

Our study provides an overview of GCA rates and late-stage diagnosis in the United States, Texas, and South Texas (STX) from 2004 to 2016 among Latinos and non-Latinos. Texas's exclusion from SEER data has limited previous comparative assessments of GCA incidence rates. Although Camargo and colleagues’ study reported robust data including Texas, only 7.9% of SEER-9 participants were Latinos.¹⁶ Previous studies were limited by region (El Paso County vs. Texas)¹⁹ or population examined (predominantly male veterans).²⁹ The present study used both SEER-21 and Texas Cancer Registry data, ensuring adequate representation of the standard United States, TX, and STX populations.

Consistent with prior studies,^{7, 17, 20} we found that overall GCA incidence rates in Texas and STX were higher in Latinos than in NHWs, despite lower frequencies in the state and STX region compared to the United States. Cardia GCA was more common in NHWs, contrasting with non-cardia, overlap, and not otherwise specified (NOS) in Latinos. This was also consistent with prior studies.^{19, 30, 31} An exception we found was in cardia GCA among women, which had similar rates among NHWs and Latinos. Although GC overall is a predominantly male disease, our findings indicate that additional measures are needed to target women who may be at risk for cardia GCA. Further research should identify such measures, as well as specific populations of women at higher risk.

Non-cardia, overlap, and NOS GCA were disproportionately represented among Latinos in all regions compared to non-Latinos. The high H. pylori infection rate in Latinos^{32, 33} coupled with H. pylori being the most well-known risk factor for more distal stomach cancers,³⁴ may account for this disparity.

In contrast to overall GCA, late-stage diagnosis odds were significantly higher in the United States than both Texas (not including STX) and STX. Texas providers may screen earlier due to the higher overall GCA prevalence in Texas and STX. This possibility can be explored in future studies. Furthermore, younger patients, those with overlapping and NOS lesions and those diagnosed during 2012–2016 had significantly higher odds of late-stage diagnosis than patients aged 65+, those with cardia GCA, and those diagnosed during 2004–2007, respectively. The increase in younger patients with GCA partially reflects previous studies, though these did not focus on late-stage disease.^8-10 To the best of our knowledge, we are the first to report this finding. This along with the increased late-stage diagnoses of overlap and NOS lesions is a disturbing indication of the lack of standardized screening practices for GC, unlike those for colorectal, breast, and ovarian cancers. The guidelines for surveillance of precursor conditions like intestinal metaplasia are based on predominantly low-quality evidence,³⁵ and only symptomatic patients are recommended to be tested for H. pylori in lower prevalence countries like the United States.³⁴ Our results support the need for development of effective methodologies of early GC screening in the United States.³⁶

None of the county-level risk factors contributed to higher odds of late-stage disease in the main analysis. Smoking was associated with decreased odds of late-stage disease in the main and anatomic site analyses. While counterintuitive, this is consistent with previous studies,^{1, 6} including a recent population-based cohort study of SEER data from 2007 to 2015 which found that Latinos with non-cardia GC were less likely to reside in counties with high smoking prevalence.⁹ As stated by Gnaldi and colleagues, in the case of disagreement between results from studies conducted at different levels, additional research is needed before it can be concluded that estimates including ecological variables are inappropriate.³⁷ It is also possible that smokers are screened earlier and thus their disease is caught earlier. However, confirming this is beyond the scope of this paper. In contrast, in the model stratified by location, STX smokers had a significantly increased risk of late-stage GCA. This is not explained by the current smoking prevalence rates in STX and TX counties, which are significantly lower than the nation (15.7% vs. 17.7%, p < 0.001; data not shown).

We explored socioeconomic status's connection to late-stage GCA using the SDI, a more complex measure than poverty alone. For the full model, SDI was not significantly associated with late-stage disease, but in the stratified model by location, only in TX without STX patients living in counties with medium and high SDI were associated with increased odds of late-stage GCA compared to those with the lowest SDI. This was surprising, given the high poverty rate in STX (~22% below 150% of the federal poverty line in 2018 vs. 12% in the United States). In contrast, in the model stratified by anatomic site, living in a county with medium SDI in STX only was associated with increased odds of NOS late-stage GCA specifically. Additional studies, preferably using individual-level data, are required to adequately characterize the interplay of SDI with H. pylori infection, which has been linked to lower socioeconomic class,³⁸ in TX and STX.

The lack of significant county-level behavioral results for late-stage disease, except for smoking, in STX is surprising, considering the high proportion of Latino residents and high prevalence of relevant risk factors. This may be due to the smaller sample size. Underdiagnosis is also a possibility, which must be further pursued.

The stratification of our data by anatomic site (e.g., cardia, non-cardia) is consistent with findings from The Cancer Genome Atlas molecular classification of GCAs.³⁹ The inclusion of overlapping and NOS GCA lesions as separate categories is justified, given the significant disparities seen across all regions, and to the best of our knowledge is the first analysis of these anatomic sites.

One strength of this study lies in extracting data from both SEER and TCR, enabling us to obtain precise rates and risk estimations in all geographic regions analyzed with the same methodology, making relevant comparisons between populations possible. Another strength is our multilevel approach using county-level GCA risk factors, including smoking, obesity, excessive alcohol consumption, food environment, and social deprivation. This allowed for a richer comparison between groups. However, one limitation is that both registries consider Latinos as a single group, which prevented us from identifying differences by ethnic subgroups. However, 88% of Texas Latinos are of Mexican origin, so data from Texas and STX may well represent this specific Latino subgroup.¹¹ Additionally, SEER and NAACCR do not have identical completeness requirements and thus have differences in organization. This may account for histology differences observed. County-level indicators (SDI, CHR variables) may not accurately describe individual-level living conditions and risk factors and warrant careful interpretation as they can lead to the ecological fallacy. While previous research has shown that smaller area estimates are better proxies for individual-level characteristics,^{40, 41} using county-level indicators are a first step in identifying additional factors not typically included in registry data. Further examination of our findings based on county-level variables is warranted, ideally with individual-level data. Additionally, county-level variables were measured at one time point only, which may not overlap with patients’ year of diagnosis. We conducted sensitivity analyses to address the limitation of county-level variables to the years 2011–2015, the range for which the SDI is available. Our findings regarding smoking prevalence for patients in STX was confirmed with the significantly reduced sample. Our sample contained approximately 11% of patients with unknown stage, who we excluded from our main analysis. As part of our sensitivity analysis, we included those with unknown stage as part of the reference group in our late-stage outcome variable. TCR had higher rates of unknown stage than SEER (14.1% vs. 9.5%), and in a previous study the type of the reporting source predicted the unknown stage.²⁸ We included reporting source in all analyses to account for reporting differences. Our sensitivity analyses including unknown stage in the analytic sample produced similar results.

As the US Latino population continues to grow, the higher GCA incidence in Latinos, particularly of late-stage disease, which is less responsive to therapy, is an increasingly important public health concern. Future studies should include genetic factors, which was beyond the scope of this paper, and interactions between alcohol consumption and social deprivation as contributors to late-stage GCA.

CONFLICT OF INTEREST

The authors declare that they have no conflict of interest.