Infection with Helicobacter pylori (H. pylori) has been identified as a risk factor for stomach cancer. H. pylori strains can be divided into two phenotypes with respect to the presence of the cytotoxin-associated gene A (cagA). Infection with cagA-positive H. pylori has been found to be more strongly associated with an increased risk of stomach cancer, especially the intestinal-type, than infection with cagA-negative H. pylori. The applicants hypothesize that cagA-positive H. pylori in particular causes increased proliferation of the gastric epithelium leading to a higher frequency and distinct pattern of molecular and cellular abnormalities. To test this hypothesis, they propose to collect formalin-fixed, paraffin-embedded tissues from 150 stomach cancer patients and 50 patients whose stomach tissues were removed due to diagnosis other than gastric cancer or peptic ulcer disease (non- tumor controls). These patients will be selected from the participants of the multiphasic health checkup at Kaiser Permanente Medical Care Program. They will analyze them for p53 mutation (by single strand conformation polymorphism and direct DNA sequencing), cell proliferation index (by immunohistochemical staining with MIB1 antibody against Ki-67 antigen), and apoptotic index (by TUNEL method). H. pylori and cagA status will be determined serologically by enzyme-linked immunosorbent assays. p53 mutation (frequency and spectrum), cell proliferation and apoptotic indices will be compared according to the cagA status and histologic type of the cancer.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA073011-02
Application #
2633956
Study Section
Metabolic Pathology Study Section (MEP)
Program Officer
Patel, Appasaheb1 R
Project Start
1997-01-25
Project End
2000-12-31
Budget Start
1998-01-01
Budget End
1998-12-31
Support Year
2
Fiscal Year
1998
Total Cost
Indirect Cost
Name
Stanford University
Department
Miscellaneous
Type
Schools of Medicine
DUNS #
800771545
City
Stanford
State
CA
Country
United States
Zip Code
94305
Shibata, Atsuko; Parsonnet, Julie; Longacre, Teri A et al. (2002) CagA status of Helicobacter pylori infection and p53 gene mutations in gastric adenocarcinoma. Carcinogenesis 23:419-24
Shibata, A; Longacre, T A; Puligandla, B et al. (2001) Histological classification of gastric adenocarcinoma for epidemiological research: concordance between pathologists. Cancer Epidemiol Biomarkers Prev 10:75-8