Polymorphisms in genes related to bacterial lipopolysaccharide/peptidoglycan signaling and gastric precancerous lesions in a population at high risk for gastric cancer.
As Helicobacter pylori (HP) is a Gram-negative bacterium, we investigated the associations between several functional polymorphisms in genes involved in lipopolysaccharide (LPS) signaling and the prevalence of various stages of gastric premalignant lesions in a Venezuelan population. The two NOD2 polymorphisms, del3020insC and Gly908Arg, were too infrequent to study their associations with gastric lesions. The risk of intestinal metaplasia (IM) was significantly increased among subjects with the CD14 T-260 allele compared to those without this allele. A similar, but nonsignificant increase in risk for dysplasia was observed among homozygotes of this allele. There was no association between TLR4 Asp299Gly polymorphism and any type of lesions, except for a slight nonsignificant increase in risk of IM associated with the AA genotype among subjects with a higher histological HP score. These results suggest that genetic polymorphisms in HP LPS signaling may be implicated in the development of intermediate stages of gastric premalignant lesions.
Kato
Ikuko
I
Karmanos Cancer Institute, 110 East Warren Avenue, Detroit, Michigan 48201, USA. katoi@med.wayne.edu
Canzian
Federico
F
Plummer
Martyn
M
Franceschi
Silvia
S
van Doorn
Leen-Jan
LJ
Vivas
Jorge
J
Lopez
Gladys
G
Lu
Yanhui
Y
Gioia-Patricola
Lydie
L
Severson
Richard K
RK
Schwartz
Ann G
AG
Muñoz
Nubia
N
D000328:Adult; D005260:Female; D005773:Gastroscopy; D005838:Genotype; D016481:Helicobacter Infections; D016480:Helicobacter pylori / Q000235:genetics*; D006801:Humans; D018950:Lipopolysaccharide Receptors / Q000235:genetics*; D008070:Lipopolysaccharides / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D053473:Nod2 Signaling Adaptor Protein / Q000378:metabolism*; D010457:Peptidoglycan / Q000378:metabolism*; D011110:Polymorphism, Genetic; D011230:Precancerous Conditions / Q000235:genetics*; D013274:Stomach Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000382:microbiology; D051197:Toll-Like Receptor 4 / Q000235:genetics*; D014687:Venezuela / Q000453:epidemiology
D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein; D010457:Peptidoglycan; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4