Dataset Information

Association of polymorphism of PTPN 11 encoding SHP-2 with gastric atrophy but not gastric cancer in Helicobacter pylori seropositive Chinese population.

ABSTRACT: BACKGROUND: The interaction between Src homology 2 domain-containing protein tyrosine phosphatase (SHP-2) of gastric epithelial cells and cagA from H. pylori plays a crucial role in developments of gastric atrophy and gastric cancer. This study aimed to investigate the association of haplotype tagging SNPs (htSNPs) in the PTPN11 gene encoding SHP-2 with gastric atrophy and gastric cancer in Chinese population. METHODS: The subjects comprised 414 patients with gastric cancer, 109 individuals with gastric atrophy and 923 healthy controls. Blood was collected from October 2008 to October 2010. Five htSNPs rs2301756, rs12423190, rs12229892, rs7958372 and rs4767860 from the PTPN11 gene were selected and genotyped by Taqman assay. Serum Ig G antibodies to H. pylori were detected by ELISA. Gastric atrophy was screened by the levels of serum pepsinogenIandII, and confirmed by endoscopy and histopatholgical examinations. Odds ratio (ORs) and 95% confidence intervals (CIs) were calculated by a multivariate logistic regression. RESULTS: Among H. pylori seropositive subjects, age and gender-adjusted OR of gastric atrophy was 2.47 (95%CI 1.13-4.55, P?=?0.02) for CC genotype compared with CT/TT genotypes, suggesting a recessive model of genetic risk for rs12423190. The prevalence of H. pylori seropositivity were significantly higher in groups of gastric cancer and gastric atrophy compared to the control group (70.3% vs. 75.2% vs. 49.7%, P <0.001). However, the distributions of genotypes and haplotypes in patients with gastric cancer were not significantly different from healthy controls. CONCLUSIONS: Our study provides the first evidence that rs12423190 polymorphism of the PTPN11 gene is significantly associated with an increased risk of gastric atrophy in H. pylori infected Chinese Han population, suggesting that rs12423190 polymorphism could be used as a useful marker of genetic susceptibility to gastric atrophy among H. pylori infected subjects. The biological roles of this polymorphism require a further investigation.

SUBMITTER: Jiang J

PROVIDER: S-EPMC3509400 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Association of polymorphism of PTPN 11 encoding SHP-2 with gastric atrophy but not gastric cancer in Helicobacter pylori seropositive Chinese population.

Jiang Jing J Jia Zhi-Fang ZF Kong Fei F Jin Mei-Shan MS Wang Yin-Ping YP Tian Suyan S Suo Jian J Cao Xueyuan X

BMC gastroenterology 20120712

<h4>Background</h4>The interaction between Src homology 2 domain-containing protein tyrosine phosphatase (SHP-2) of gastric epithelial cells and cagA from H. pylori plays a crucial role in developments of gastric atrophy and gastric cancer. This study aimed to investigate the association of haplotype tagging SNPs (htSNPs) in the PTPN11 gene encoding SHP-2 with gastric atrophy and gastric cancer in Chinese population.<h4>Methods</h4>The subjects comprised 414 patients with gastric cancer, 109 ind ...[more]

PMID: 22788847

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Project description:BackgroundRegional variations in gastric cancer incidence are not explained by prevalence of Helicobacter pylori, the main cause of the disease, with several areas presenting high H. pylori prevalence but low gastric cancer incidence. The IARC worldwide H. pylori prevalence surveys (ENIGMA) aim at systematically describing age and sex-specific prevalence of H. pylori infection around the world and generating hypotheses to explain regional variations in gastric cancer risk.MethodsWe selected age- and sex-stratified population samples in two areas with different gastric cancer incidence and mortality in Chile: Antofagasta (lower rate) and Valdivia (higher rate). Participants were 1-69 years old and provided interviews and blood for anti-H. pylori antibodies (IgG, VacA, CagA, others) and atrophy biomarkers (pepsinogens).ResultsH. pylori seroprevalence (Age-standardized to world population) and antibodies against CagA and VacA were similar in both sites. H. pylori seroprevalence was 20% among children <10 years old, 40% among 10-19 year olds, 60% in the 20-29 year olds and close to or above 80% in those 30+ years. The comparison of the prevalence of known and potential H. pylori cofactors in gastric carcinogenesis between the high and the low risk area showed that consumption of chili products was significantly higher in Valdivia and daily non-green vegetable consumption was more common in Antofagasta. Pepsinogen levels suggestive of gastric atrophy were significantly more common and occurred at earlier ages in Valdivia, the higher risk area. In a multivariate model combining both study sites, age, chili consumption and CagA were the main risk factors for gastric atrophy.ConclusionsThe prevalence of H. pylori infection and its virulence factors was similar in the high and the low risk area, but atrophy was more common and occurred at younger ages in the higher risk area. Dietary factors could partly explain higher rates of atrophy and gastric cancer in Valdivia.ImpactThe ENIGMA study in Chile contributes to better understanding regional variations in gastric cancer incidence and provides essential information for public health interventions.

Dataset Information

Association of polymorphism of PTPN 11 encoding SHP-2 with gastric atrophy but not gastric cancer in Helicobacter pylori seropositive Chinese population.

Publications

Association of polymorphism of PTPN 11 encoding SHP-2 with gastric atrophy but not gastric cancer in Helicobacter pylori seropositive Chinese population.

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