Although gastric cancer mortality rates are gradually decreasing around the world, there are countries, especially in East Asia in which this disease remains prevalent. Helicobacter pylori colonization has been strongly associated with gastric cancer in cohort and case-control studies. Until now, most studies have reported an association between H. pylori and gastric cancer using serological surveys with pools of cell surface preparations from the bacteria as the antigen. However, H. pylori isolates from different geographic areas vary in genotype. We propose to design specific antigenic regions from the major virulence marker of H. pylori (VacA), and by assessing the immune response to this bacterial antigen, determine whether it is a better predictor for the risk of development of gastric cancer in selected populations. For VacA we will obtain peptide antigens specific for the mid region (m1 and m2) because preliminary data suggests that differences in this region may be a predictor of the development of gastric cancer. From a nested case-control study of Japanese-Americans in Hawaii, serum samples were obtained from individuals before they developed gastric cancer over a 21-year follow-up. We also have serum samples from control individuals who did not develop gastric cancer. We expect to find that the immune response to one particular vacA genotype (m1) is predominantly observed in those patients who developed gastric cancer compared to those in whom gastric cancer did not develop. If our hypothesis is correct, we hope to establish a simple and economical serological test to assess the risk of gastric cancer development.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Small Research Grants (R03)
Project #
5R03CA099512-02
Application #
6787641
Study Section
Special Emphasis Panel (ZCA1-SRRB-Q (M1))
Program Officer
Starks, Vaurice
Project Start
2003-08-06
Project End
2005-03-31
Budget Start
2004-04-01
Budget End
2005-03-31
Support Year
2
Fiscal Year
2004
Total Cost
$84,500
Indirect Cost
Name
New York University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
121911077
City
New York
State
NY
Country
United States
Zip Code
10016
Ghose, Chandrabali; Perez-Perez, Guillermo I; Torres, Victor J et al. (2007) Serological assays for identification of human gastric colonization by Helicobacter pylori strains expressing VacA m1 or m2. Clin Vaccine Immunol 14:442-50
Portal-Celhay, Cynthia; Perez-Perez, Guillermo I (2006) Immune responses to Helicobacter pylori colonization: mechanisms and clinical outcomes. Clin Sci (Lond) 110:305-14
Harris, Paul; Perez-Perez, Guillermo; Zylberberg, Alejandro et al. (2005) Relevance of adjusted cut-off values in commercial serological immunoassays for Helicobacter pylori infection in children. Dig Dis Sci 50:2103-9
Perez-Perez, Guillermo Ignacio; Olivares, Asalia Zuni; Foo, F Yeong et al. (2005) Seroprevalence of Helicobacter pylori in New York City populations originating in East Asia. J Urban Health 82:510-6