Gastric Breast Cancer Network Center

Current best practices and rationalistic perspectives in causation-based prevention, early detection and multidisciplinary treatment of breast and gastric cancer

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Prediction-Risk Model for Targeting Gastric Cancer Prevention

ABSTRACT

Approximately half of the world's population is infected by Helicobacter pylori. This inflammation of the stomach tissue will ultimately lead a small minority either to peptic ulcer or to gastric neoplasia, but the majority of infected persons (>80%) will develop no significant clinical disease in their lifetime. Thus, prediction of a high-risk subpopulation of developing cancer is the current great challenge of research.

Gastric cancer relatives (Gastroenterology (GE) 2000;118:22-30) and individuals with interleukin-1â genetic polymorphisms exposed to H. pylori are at increased risk of hypochlorhydria, atrophy and gastric cancer (Nature 2000;404:398-402, GE 2001;121:1002-4). Atrophic gastritis and intestinal metaplasia have been established as precursor lesions [NEJM 2001;345:784-9], At risk are also subjects with nonulcer dyspepsia, gastric ulcer or gastric polyps (NEJM 2001;345:784-9). However, many other yet unidentified genetic and environment factors determine the progression of these precursors to cancer.

Here we discuss all these possible genetic and epigenetic factors including bacteria gene polymorphisms and their interactions with human host (Nat Med 2000;6:376-7), micronutritients oxidants (diet) [J Natl Cancer Inst 2000;92:1881-8). Gastric cancer development is a clear example of gene-environment interaction. The exposure is responsible for the interaction with a large number of low-penetrant genes and their polymorphisms resulting in an initiation of carcinogenesis. We discuss the difficulties in the identification of these weak genes and thus the limitations of genetic screening in population (NEJM 2000;343:141-4, Lancet 2001;357:709-12).

Taken together all these data, the difficulties in performing endoscopy in asymptomatic subjects for detection of precursors, and the debatable role of H. pylori in gastroesophageal reflux disease and in cardia cancer, we developed a prediction-risk model that facilitates a medical decision for target prevention.

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