Abstract
BackgroundGeospatial technology has facilitated the discovery of disease distributions and etiology and helped target prevention programs. Globally, gastric cancer is the leading infection-associated cancer, and third leading cause of cancer mortality worldwide, with marked geographic variation. Central and South America have a significant burden, particularly in the mountainous regions. In the context of an ongoing population-based case-control study in Central America, our aim was to examine the spatial epidemiology of gastric cancer subtypes and H. pylori virulence factors.MethodsPatients diagnosed with gastric cancer from 2002 to 2013 in western Honduras were identified in the prospective gastric cancer registry at the principal district hospital. Diagnosis was based on endoscopy and confirmatory histopathology. Geospatial methods were applied using the ArcGIS v10.3.1 and SaTScan v9.4.2 platforms to examine regional distributions of the gastric cancer histologic subtypes (Lauren classification), and the H. pylori CagA virulence factor. Getis-Ord-Gi hot spot and Discrete Poisson SaTScan statistics, respectively, were used to explore spatial clustering at the village level (30–50 rural households), with standardization by each village’s population. H. pylori and CagA serologic status was determined using the novel H. pylori multiplex assay (DKFZ, Germany).ResultsThree hundred seventy-eight incident cases met the inclusion criteria (mean age 63.7, male 66.3%). Areas of higher gastric cancer incidence were identified. Significant spatial clustering of diffuse histology adenocarcinoma was revealed both by the Getis-Ord-GI* hot spot analysis (P-value < 0.0015; range 0.00003–0.0014; 99%CI), and by the SaTScan statistic (P-value < 0.006; range 0.0026–0.0054). The intestinal subtype was randomly distributed. H. pylori CagA had significant spatial clustering only in association with the diffuse histology cancer hot spot (Getis-Ord-Gi* P value ≤0.001; range 0.0001–0.0010; SaTScan statistic P value 0.0085). In the diffuse gastric cancer hot spot, the lowest age quartile range was 21–46 years, significantly lower than the intestinal cancers (P = 0.024).ConclusionsGeospatial methods have identified a significant cluster of incident diffuse type adenocarcinoma cases in rural Central America, suggest of a germline genetic association. Further genomic and geospatial analyses to identify potential spatial patterns of genetic, bacterial, and environmental risk factors may be informative.
Highlights
Geospatial technology has facilitated the discovery of disease distributions and etiology and helped target prevention programs
The study was set in rural Honduras and is representative of the Central America Four (“Central America Four region (CA-4)”) region (Guatemala, Honduras, El Salvador, Nicaragua), the largest low/middle income countries (LMICs) region in the western hemisphere, with over 36 million inhabitants [26]
We prospectively identified all incident cases of gastric cancer between 2002 and 2013 from a registry within the Ministry of Health district hospital (Hospital de Occidente) of western Honduras in Santa Rosa de Copán, that serves as the principal referral center for the region
Summary
Geospatial technology has facilitated the discovery of disease distributions and etiology and helped target prevention programs. Gastric cancer is the leading infection-associated cancer, and third leading cause of cancer mortality worldwide, with marked geographic variation. In the context of an ongoing population-based casecontrol study in Central America, our aim was to examine the spatial epidemiology of gastric cancer subtypes and H. pylori virulence factors. Gastric adenocarcinoma is the leading global cause of infection-related cancer mortality and overall is the third leading cause of cancer death [1,2,3,4]. In Latin America, a significant burden of disease is concentrated in the mountainous regions along the Pacific littoral [6, 7], the gastric cancer “altitude enigma”, and may represent host genetic variation. H. pylori CagA has been shown to be an important virulence factor for disease progression to gastric adenocarcinoma [13,14,15,16]. The principal subsets of gastric adenocarcinoma per the Lauren histologic classification are intestinal and diffuse, and recent findings in The Cancer Genome Atlas (TCGA) NIH initiative confirm these subtypes [17,18,19]
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