Research & Development

 Gastric Cancer Research Program
 Dr. Ricardo Domínguez, an internal medicine specialist in western Honduras, has watched local trends in stomach cancer for the last decade.  He and several Honduran colleagues conducted a long-term gastric cancer study.  Recently Dr. Domínguez and gastroenterologist Dr. Doug Morgan, of the University of North Carolina, began to analyze that information and plan for an extended  project to develop the detection and prevention of gastric cancer in Honduras.  There is a very high incidence of death due to stomach cancer in western Honduras.  Through the work of dedicated physicians like Drs. Domínguez and Morgan, CAMO is helping in the fight against gastric cancer.

 Medical professionals join CAMO every  year to assist in the research and development of our many programs.  At this time the Laboratory, Radiology, Emergency and  general hospital operations are key areas of study.
  

Do You Have a Resource to Share?
Interested medical professionals are encouraged to contact the CAMO office for further information on our programs and human resources needs.  Medical professionals contribute their skills at home and abroad. If you would like to help fund an education program, CAMO staff is happy to discuss the various areas of development and specific program needs. 
 

Donated funds can be designated  in the following areas: : Collection of equipment Volunteer travel costs Equipment repairs  Overseas education Shipment of supplies Project research

BACKROUND. Gastric cancer is the second leading cause of cancer morbidity and mortality in the world with significant geographic variability. Interleukin-1B genotypes (-511T, -31T, -RN*2) have been associated with gastric adenocarcinoma in H. pylori infected patients in Europe and Asia. The backround prevalence of polymorphisms in these populations ranges 50-70% (-511T; CT, 39-50%; TT, 11-21%). A systematic evaluation of gastric cancer risk factors (host genetic, bacterial, dietary, environmental) within a population-based study design is lacking. 

METHODS. The current study is a prospective, population-based, case-control design in western Honduras, Central America. The western region of Honduras (population ½ million, 95% Hispanic mestizo) has been newly identified as having a high incidence of gastric cancer. In a recent 10-year retrospective survey, the estimated standardized gastric cancer incidence rate for the year 2000 was 39 and 21 for males and females, respectively (per 100,000 world standard population). Nearly one quarter of cases occurred below the age of 50, with about 12% under the age of 35. 
In the current study, gastric cancer cases were enrolled in prospective fashion from the Western Regional Hospital Endoscopy Unit. Satellite imagery from the Honduran Municipality Community Development Department (from UNESCO) facilitated a population-based approach to control recruitment. Controls were balanced among the sexes and age ranges (18-34, 35-49, 50-64, >65). Genomic DNA was obtained from whole blood per protocol (Gentra Systems) H. pylori status was established by ELISA serology (Meridian Bioscience). Gastric cancer cases were confirmed by histology. The image-based DietHistory® was used to establish dietary and micronutrient intake. 

RESULTS. At present, 120 subjects have been enrolled (35 gastric cancer cases, 85 controls), with interim study data available for 51 subjects (12 cases, 39 controls). Striking genetic susceptibility of the general population is observed, with the IL-1B–511T prevalence of 98% (95% CI, 92-100%) in the controls. This includes heterozygotes and homozygotes frequencies of 62%(CT) and 36%(TT), respectively, unique in the world. Prevalence is similar in the cancer group. Endemic H. pylori infection is confirmed (86%). Initial analysis of the DietHistory® data reveals successful nutritional data acquisition. Significant intake deficiencies are noted among cancer patients with alphacarotene, lycopene, and selenium. 

CONCLUSIONS. Endemic gastric cancer genetic susceptibility is noted in the population of Western Honduras, using population-based techniques. Further analysis of population genetic susceptibility (eg, -RN*2), bacterial virulence factors, and dietary cofactors is indicated. Design of a region-appropriate gastric cancer screening program is warranted. 

BACKROUND. Gastric cancer is the second leading cause of cancer morbidity and mortality in the world with significant geographic variability. Proinflammatory cytokine gene polymorphisms (IL-IB, IL-1RA, IL-10, TNF-A) have been associated with noncardia gastric adenocarcinoma in H. pylori infected patients in Europe and Asia. Carriage of multiple cytokine genotypes confers increased cancer risk. The backround prevalence of polymorphisms in these populations ranges 50%-70% (IL-IB -511T: CT, 39-50%; TT, 4-21% and IL-10-1082: GA, 49%, AA, 28%). A systematic evaluation of gastric cancer risk factors (host genetic, bacterial, dietary) within a population-based study design is lacking. 

METHODS. The current study is a prospective, population-based, case-control design in western Honduras, Central America. The western region of Honduras (population ½ million, 95% Hispanic mestizo) has been newly identified as having a high incidence of gastric cancer. In a recent 10-year retrospective survey, the estimated standardized gastric cancer incidence rate for the year 2000 was 39 and 21 for males and females, respectively (per 100,000 world standard population). Nearly one quarter of cases occurred below the age of 50, with about 12% under the age of 35. 
In the current study, gastric cancer cases were enrolled in prospective fashion from the Western Regional Hospital Endoscopy Unit. Satellite imagery from the Honduran Municipality Community Development Department (from UNESCO) facilitated a population-based approach to control recruitment. Controls were balanced among the sexes and age ranges (18-34, 35-49, 50-64, >65). Genomic DNA was obtained from whole blood per protocol (Gentra Systems) H. pylori status was established by ELISA serology (Meridian Bioscience). Gastric cancer cases were diagnosed by endoscopy and confirmatory histology. 

The image-based DietHistory® was used to establish dietary and micronutrient intake. 

RESULTS. At present, 234 subjects have been enrolled (115 gastric cancer cases, 119 controls), with interim study data available for 175 subjects (110 controls, 65 cases). Striking genetic susceptibility of the general population is observed, unique in the world. In the controls, the IL-1B–511T+ prevalence is 84% (95% CI, 80-90%), with heterozygote and homozygote frequencies of 56.5%(CT) and 27%(TT), respectively. The IL-10-1082A+ is 93%, with heterozygote and homozygote frequencies of 33%(GA) and 60%(AA), respectively. Prevalence is similar in the cancer group. Endemic H. pylori infection is confirmed (88%). 
Haplotype analysis suggests that 89% of the general population demonstrates a significantly increased risk for gastric adenocarcinoma. Risk is moderately increased in 27% of controls (OR 2-5; CC/AA, CT/GG, CT/GA), and markedly increased in 62% (OR 5-10; CT/AA, TT/GG, TT/A*). Over 18% of the population is homozygotic for both the IL-1B and IL-10 polymorphisms, while less than 1% carries the wild type for the alleles. 

Initial analysis of the DietHistory® data reveals successful nutritional data acquisition. Significant intake deficiencies are noted among cancer patients with alphacarotene, lycopene, and selenium. 

CONCLUSIONS. A unique global population has been identified, with endemic gastric cancer genetic susceptibility, manifest by the high prevalence of proinflammatory cytokine gene polymorphisms in the setting of endemic H. pylori infection. Further analysis of population genetic susceptibility, bacterial virulence factors, and dietary cofactors is indicated. 
Design of a region-appropriate gastric cancer screening program is warranted.

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