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Association of NOD1 and NOD2 genes polymorphisms with Helicobacter pylori related gastric cancer in a Chinese population.

ABSTRACT: To investigate the association between the tag single nucleotide polymorphisms (TagSNPs) of NOD1 and NOD2 and the risk of developing gastric cancer.We conducted a hospital-based case-control study including 296 incident gastric cancer patients and 160 gastritis controls. Eight TagSNPs in the NOD1 and NOD2 genes were selected from the Hapmap database using the haploview software and genotyped by the Sequenom MassArray system. The serum levels of anti-Helicobacter pylori (H. pylori) IgG were measured by enzyme-linked immunosorbent assay to indicate H. pylori infection. The odds ratios (OR) and 95% confidence intervals (CI) were calculated by unconditional logistic regression, including sex and age as confounding factors.The NOD1 rs2907749 GG genotype showed a decreased risk for gastric cancer (OR 0.50, 95% CI: 0.26-0.95, P = 0.04) while the rs7789045 TT genotype showed an increased risk (OR 2.14, 95% CI: 1.20-3.82, P = 0.01). An elevated susceptibility to gastric cancer was observed in the subjects with H. pylori infection and the NaOD1 rs7789045 TT genotype (OR 2.05, 95% CI: 1.07-3.94, P = 0.03) or the NOD2 rs7205423 GC genotype (OR 2.52, 95% CI: 1.05-6.04, P = 0.04). Haplotype analysis suggested that the distribution of AGT (rs2907749, rs2075820 and rs7789045) in NOD1 between the cases and control groups was significantly different (P corrected: 0.04), and the diplotype AGT/AGT was associated with an elevated gastric cancer risk (OR 1.98, 95% CI: 1.04-3.79, P = 0.04). The association of the NOD1 rs7789045 TT genotype and the diplotype AGT/AGT was significant with H. pylori-related diffuse-type gastric cancer (OR 3.00, 95% CI: 1.38-6.53, P = 0.01; OR 4.02, 95% CI: 1.61-10.05, P < 0.01, respectively).Genetic polymorphisms in NOD1 and NOD2 may interact with H. pylori infection and may play important roles in promoting the development of gastric cancer in the Chinese population.

SUBMITTER: Wang P

PROVIDER: S-EPMC3342611 | biostudies-literature | 2012 May

REPOSITORIES: biostudies-literature

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Association of NOD1 and NOD2 genes polymorphisms with Helicobacter pylori related gastric cancer in a Chinese population.

Wang Peng P Zhang Li L Jiang Jian-Ming JM Ma Dan D Tao Hao-Xia HX Yuan Sheng-Ling SL Wang Yan-Chun YC Wang Ling-Chun LC Liang Hao H Zhang Zhao-Shan ZS Liu Chun-Jie CJ

World journal of gastroenterology 20120501 17

<h4>Aim</h4>To investigate the association between the tag single nucleotide polymorphisms (TagSNPs) of NOD1 and NOD2 and the risk of developing gastric cancer.<h4>Methods</h4>We conducted a hospital-based case-control study including 296 incident gastric cancer patients and 160 gastritis controls. Eight TagSNPs in the NOD1 and NOD2 genes were selected from the Hapmap database using the haploview software and genotyped by the Sequenom MassArray system. The serum levels of anti-Helicobacter pylor ...[more]

PMID: 22563200

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Project description:BackgroundThe 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.MethodsThe 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.ResultsAmong 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.ConclusionsOur 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.

Project description:BackgroundHIV and Helicobacter pylori are common chronic infections in sub-Saharan Africa. Both conditions can predispose to gastric hypochlorhydria that may be a risk factor for enteric infections and reduced drug absorption. We have investigated to what extent HIV and H. pylori infections are associated with hypochlorhydria in a Malawian cohort of patients undergoing endoscopy.Methods104 sequential symptomatic adults referred for gastroscopy at Queen Elizabeth Central Hospital, Blantyre, Malawi, had blood taken for rapid HIV testing and fasting serum gastrin analysis. Gastric fluid was aspirated for pH testing, and gastric biopsies were taken.ResultsAfter 9/104 HIV-infected patients who were already established on anti-retroviral therapy were excluded, 17/95 (25.0%) were seropositive for untreated HIV, and 68/95 (71.6%) patients were H. pylori positive by histology. Hypochlorhydria (fasting gastric pH>4.0) was present in 55.8% (53/95) of patients. H. pylori infection was significantly associated with hypochlorhydria (OR 2.91, [1.02-7.75], p=0.046). While single infection with HIV was not significantly independently associated with hypochlorhydria. H. pylori and HIV co-infection was more strongly associated with hypochlorhydria (OR 6.25, [1.33-29.43], p=0.020) than either infection alone, suggesting an additive effect of co-infection. HIV infection was associated with higher serum gastrin levels (91.3 pM vs. 53.1 pM, p=0.040), while H. pylori infection was not (63.1 pM vs. 55.1 pM, p=0.610). Irrespective of H. pylori and HIV status, most patients (>90%) exhibited pangastritis. Only three patients had histological evidence of gastric atrophy, of which only one was HIV-infected.ConclusionH. pylori infection was associated with fasting hypochlorhydria, while HIV was not independently associated. HIV and H. pylori co-infection, however, was more strongly associated with hypochlorhydria than H. pylori infection alone. The mechanism of this apparent additive effect between HIV and H. pylori remains unclear, but appears to be related to chronic pangastritis rather than gastric atrophy, and associated with hypergastrinaemia in HIV-infected individuals.

Dataset Information

Association of NOD1 and NOD2 genes polymorphisms with Helicobacter pylori related gastric cancer in a Chinese population.

Publications

Association of NOD1 and NOD2 genes polymorphisms with Helicobacter pylori related gastric cancer in a Chinese population.

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