BIOLOGICAL MARKERS OF H PYLORI INDUCED ONCOGENESIS

Project Details

Description

Adenocarcinoma of the stomach is one second most common cause of cancer
mortality in the world, and epidemiologic studies have indicated that
early-life exposure to an environmental agent is associated with later
cancer risk. Once acquired, Helicobacter pylori causes chronic superficial
gastritis, and is the major cause for this process throughout the world.
Previous work indicates that chronic superficial gastritis may progress to
atrophic gastritis, which in some cases leads to cancer. A wide variety of
data indicate the biological plausibility of persistent H. pylori
infection playing a role in pathogenesis of gastric cancer, and several
epidemiologic studies have demonstrated a direct association. A growing
body of evidence suggests that intensity of inflammation and heightened
humoral response to H. pylori enhance cancer risk. However, most H.
pylori-infected persons do not develop gastric cancer. The purpose of the
proposed study is to identify further H. pylori-linked markers for persons
at high or low risk of developing gastric cancer. Serum and gastric
tissue specimens have been acquired from three previous studies
(Minnesota, Hawaii, Japan) in which an association of H. pylori infection
and gastric cancer have been shown, and from villagers in Shandong
Province in China who differ substantially in cancer risk. Using these
specimens, we will address three hypotheses concerning risk of developing
gastric cancer. First, that strain-specific H. pylori characteristics
affect risk. We will focus on alleles of vacA, the gene encoding the
vacuolating cytotoxin, since previous data indicate that in vitro
expression of toxin production is associated with enhanced inflammation.
Second, that host responses to conserved H. pylori antigens represent
markers for risk. We will explore the relationship of serum IgA and IgG
responses to conserved antigens including the hspA and hspB products.
Third, we will explore whether specific host tissue responses to H. pylori
antigens are risk factors. Utilizing blocks of unaffected gastric tissue
from cancer patients and controls, we will explore whether H. pylori-
induced production of pro-inflammatory cytokines or growth factors is
associated with disease outcome. From these studies, we hope to define
markers for gastric cancer risk as well as to better understand
intermediate mechanisms in its pathogenesis.
StatusFinished
Effective start/end date9/30/958/31/99

Funding

  • National Institute of Diabetes and Digestive and Kidney Diseases

ASJC

  • Oncology
  • Cancer Research

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