Interleukin-1 polymorphisms associated with increased risk of gastric cancer.
Helicobacter pylori infection is associated with a variety of clinical outcomes including gastric cancer and duodenal ulcer disease. The reasons for this variation are not clear, but the gastric physiological response is influenced by the severity and anatomical distribution of gastritis induced by H. pylori. Thus, individuals with gastritis predominantly localized to the antrum retain normal (or even high) acid secretion, whereas individuals with extensive corpus gastritis develop hypochlorhydria and gastric atrophy, which are presumptive precursors of gastric cancer. Here we report that interleukin-1 gene cluster polymorphisms suspected of enhancing production of interleukin-1-beta are associated with an increased risk of both hypochlorhydria induced by H. pylori and gastric cancer. Two of these polymorphism are in near-complete linkage disequilibrium and one is a TATA-box polymorphism that markedly affects DNA-protein interactions in vitro. The association with disease may be explained by the biological properties of interleukin-1-beta, which is an important pro-inflammatory cytokine and a powerful inhibitor of gastric acid secretion. Host genetic factors that affect interleukin-1-beta may determine why some individuals infected with H. pylori develop gastric cancer while others do not.
El-Omar
E M
EM
Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, USA. elomare@mail.nih.gov
Carrington
M
M
Chow
W H
WH
McColl
K E
KE
Bream
J H
JH
Young
H A
HA
Herrera
J
J
Lissowska
J
J
Yuan
C C
CC
Rothman
N
N
Lanyon
G
G
Martin
M
M
Fraumeni
J F
JF
Rabkin
C S
CS
D000483:Alleles; D016022:Case-Control Studies; D015331:Cohort Studies; D005744:Gastric Acid / Q000378:metabolism; D005756:Gastritis / Q000150:complications / Q000276:immunology / Q000382:microbiology; D005787:Gene Frequency; D005838:Genotype; D016481:Helicobacter Infections / Q000150:complications* / Q000276:immunology; D016480:Helicobacter pylori; D006801:Humans; D007375:Interleukin-1 / Q000235:genetics*; D015810:Linkage Disequilibrium; D005810:Multigene Family; D011110:Polymorphism, Genetic; D012307:Risk Factors; D013274:Stomach Neoplasms / Q000235:genetics* / Q000276:immunology / Q000382:microbiology
D007375:Interleukin-1