Association Between Serum Pepsinogens and Polymorphismof Ptpn11 Encoding Shp-2 Among Helicobacter Pylori Seropositive Japanese.
From: Department of Gastroenterology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
International journal of cancer. Journal international du cancer
- Publish Date: Jan 2006
- ISSN: 0020-7136
- Volume: 118
- Issue: 1
- Pages: 203-8
- Medium: Print
- Language: English
- Citation (JAMA): Goto Yasuyuki, Ando Takafumi, Yamamoto Kazuhito, et al. Association Between Serum Pepsinogens and Polymorphismof Ptpn11 Encoding Shp-2 Among Helicobacter Pylori Seropositive Japanese.. Int. J. Cancer Jan 2006;118:203-8
Abstract
Helicobacter pylori (H. pylori) plays a crucial role in the development of gastric atrophy and cancer, and cagA-positive strains, which are universal in Japan, increase the risk of these outcomes substantially. The CagA protein is injected from attached H. pylori into gastric epithelial cells and undergoes Src-dependent tyrosine phosphorylation and activation of the eukaryotic phosphatase SHP-2. The CagA/SHP-2 interactions elicit cellular changes that increase the risk of carcinogenesis. We investigated the association of a frequent single nucleotide polymorphism (SNP; JST057927; G-to-A) in the PTPN11 gene that encodes SHP-2 with gastric atrophy and gastric cancer in Japan. Gastric atrophy was assessed by measuring serum pepsinogen I and II levels. The subjects comprised 454 healthy controls (126 males; mean age, 58.4) and 202 gastric cancer cases (134 males and 68 females; mean age, 66.7). All gastric cancer cases and 250 (55%) controls were H. pylori seropositive; 179 (89%) of the gastric cancer cases had gastric atrophy compared to 137 (55%) of the H. pylori seropositive controls (p < 0.001). Among HP seropositive controls compared to the common PTPN11 G/G genotype, the odds ratio of atrophy was nonsignificantly reduced with the G/A genotype (0.70; 95% CI = 0.39-1.25) and significantly reduced with the A/A genotype (0.09; 95% CI = 0.01-0.72). Lower risk for gastric atrophy had a gene-dose association with the A allele (p = 0.01, trend test). There was a clear deficiency of the A/A genotype in those with atrophy compared to those without (1 subject in the gastric atrophy group vs. 8 in the group without). Cancer cases differed from controls in frequencies of PTPN11 G/A genotype only because of a higher prevalence of atrophy among the cancer cases. The G/A SNP in the PTPN11 gene appears to be a risk factor for gastric atrophy in subjects infected with cagA-positive H. pylori. This may explain why only a proportion of CagA-positive individuals develop gastric atrophy and gastric cancer, even though infection with cagA strains is universal in Asian countries such as Japan. The functional consequences of the G/A polymorphism remain to be elucidated.
Mesh Headings (Keywords): Atrophy, Case-Control Studies, Female, Genotype, Helicobacter Infections, Helicobacter pylori, Humans, Intracellular Signaling Peptides and Proteins, Japan, Male, Middle Aged, Pepsinogen A, Pepsinogen C, Polymorphism, Single Nucleotide, Protein Tyrosine Phosphatase, Non-Receptor Type 11, Protein Tyrosine Phosphatases, Risk Factors, Stomach, Stomach Neoplasms
Check for Full Text / PubMed Unique Identifier (PMID): 16032704
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