Clinical–alimentary tractA Functional Polymorphism of Toll-Like Receptor 4 Gene Increases Risk of Gastric Carcinoma and Its Precursors
Section snippets
Study Populations
To determine whether the TLR4+896A>G polymorphism is associated with differing outcomes of H pylori infection, we studied a cohort of 149 healthy Caucasian first-degree relatives of gastric cancer patients (GCR) from the West of Scotland. These subjects had been extensively investigated in relation to their H pylori status (assessed by 14C-urea breath test, serology, rapid slide urease test, culture, and histology). Their gastric phenotype was defined histologically by assessment of antral and
Results
In all 3 control populations, the alleles at the TLR4+896 locus were in Hardy-Weinberg equilibrium, With nonsignificant χ2 values. The frequency of the variant allele in the 3 control populations ranged from 3.9% to 4.3%, and was similar to those reported from other studies of Caucasians. The homozygous TLR4+896 G/G genotype was rare, and the A/G and G/G carrier genotypes were combined in the genetic association analyses.
Discussion
In the present study, we have shown that a functional TLR4 polymorphism is associated with the development of the premalignant gastric abnormalities of hypochlorhydria and atrophy, and also with increased risk of noncardia gastric carcinoma. The association with noncardia gastric carcinoma was confirmed in 2 independent population-based case–control studies. No association was seen with cancer of the cardia or esophagus. Although this polymorphism has been associated with risk of other
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Supported by a grant from Cancer Research UK (C8969/A3868), and by the Intramural Research Program of the National Cancer Institute, National Institutes of Health.