Host polymorphisms of immune regulatory genes as risk factors for gastric cancer.
The infection of the stomach with the gram-negative bacterium Helicobacter pylori is the main risk factor for the development of gastric cancer (GC). This led to the classification of this germ as "definite carcinogen" by the World Health Organization in 1994. The current model of gastric carcinogenesis is based on the interaction of multiple risk factors including virulence factors of the bacterium (e.g. CagA, VacA), environmental factors (diet, smoking) and host factors (gene polymorphisms). The complex interplay among these factors determines the clinical outcome of the infection leading to at least one of three major diseases in 1 out of 7 infected persons, namely ulcer disease, GC and "mucosa-associated lymphoid tissue" lymphoma in 15 %, 1% and 0.1% of all persons infected with H. pylori, respectively. Recently, an increasing number of genomic polymorphisms, mostly single nucleotide polymorphisms have been identified as risk factors for gastric cancer. Among them are genes encoding for cytokines, pattern recognition receptors, cell cycle-regulators, proteases, HLA-molecules, and enzymes for detoxification. In the last years it has become clear that an uniform "genomic risk pattern" for all GC patients does not exist. Most of these host factors are restricted either to the histological type (intestinal vs. diffuse), ethnical background (particularly Caucasian vs. Asian) and tumor localization (non-cardia vs. cardia cancer). Here, we review the current knowledge about the role of host factors for the gastric carcinogenesis focusing on immune-regulatory genes, in particular on the cytokine interleukin-1beta.
Wex
T
T
Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University Magdeburg Germany. thomas.wex@med.ovgu.de
Bornschein
J
J
Malfertheiner
P
P
D002273:Carcinogens; D016207:Cytokines / Q000502:physiology; D005809:Genes, Regulator; D005838:Genotype; D016481:Helicobacter Infections; D016480:Helicobacter pylori; D006801:Humans; D007375:Interleukin-1 / Q000502:physiology; D008223:Lymphoma / Q000209:etiology; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D013274:Stomach Neoplasms / Q000453:epidemiology / Q000209:etiology* / Q000235:genetics*; D013276:Stomach Ulcer / Q000209:etiology; D014944:World Health Organization
D002273:Carcinogens; D016207:Cytokines; D007375:Interleukin-1