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.
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