Low-Positive Antibody Titer against Helicobacter pylori Cytotoxin-Associated Gene A (CagA) May Predict Future Gastric Cancer Better Than Simple Seropositivity against H. pylori CagA or against H. pylori
ABSTRACT To investigate the IgG antibody titer against Helicobacter pylori CagA as a risk factor for future noncardia gastric cancer.
A nested case-control study was done in the longitudinal cohort of atomic bomb survivors using stored sera before diagnosis (mean, 2.3 years). Enrolled were 299 cancer cases and 3 controls per case selected from cohort members matched on age, gender, city, and time and type of serum storage and countermatched on radiation dose.
H. pylori IgG seropositive with CagA IgG low titer was the strongest risk factor for noncardia gastric cancer [relative risk (RR), 3.9; 95% confidence interval (95% CI), 2.1-7.0; P < 0.001], especially for intestinal-type tumor (RR, 9.9, 95% CI, 3.5-27.4; P < 0.001), compared with other risk factors, H. pylori IgG seropositive with CagA IgG negative (RR, 2.2; 95% CI, 1.3-3.9; P = 0.0052), H. pylori IgG seropositive with CagA IgG high titer (RR, 2.0; 95% CI, 1.3-3.2; P = 0.0022), chronic atrophic gastritis (RR, 2.4; 95% CI, 1.8-3.3; P < 0.001), current smoking (RR, 2.3; 95% CI, 1.4-3.5; P < 0.001), or radiation dose (RR, 2.1; 95% CI, 1.2-3.1; P = 0.00193). Current smoking showed significantly higher risk for diffuse-type than intestinal-type tumors (P = 0.0372). Radiation risk was significant only for nonsmokers, all noncardia, and diffuse-type gastric cancers.
A low CagA IgG titer is a useful biomarker to identify a high-risk group and it also provides a clue to understanding host-pathogen interaction.
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ABSTRACT: Infection with Helicobacter pylori cytotoxin-associated gene A (CagA) positive strains is associated with the development of gastric cancer. However, some reports have failed to demonstrate an increased frequency of CagA antibodies in gastric cancer patients. We evaluated the response of IgG antibody and subclasses IgG1 and IgG2 against both, CagA and H. pylori membrane antigens in patients with precancerous lesions and cases with gastric cancer. We selected 137 patients with a positive serum IgG response to H. pylori: 46 with intestinal metaplasia, 41 with gastric adenocarcinoma and 50 with non-atrophic gastritis considered as controls. The response of total-IgG, IgG1 and IgG2 was investigated by immunoblot and ELISA using an in-house recombinant CagA and membrane antigens from a local strain, and possible associations were estimated using a logistic regression model. Compared to NAG, gastric cancer patients showed a higher frequency of IgG2 CagA antibodies (55.2% vs 15.4%, p= 0.001), but a lower frequency (80.5% vs 96.0%, p= 0.021) and diminished levels of IgG2 H. pylori antibodies (12.5 EU vs 21.9 EU, p= 0.007). Gastric cancer patients also presented lower levels of CagA (32.6 EU vs 42.4 EU, p= 0.004) and H. pylori total-IgG (33.7 EU vs 38.7 EU, p= 0.029). Gastric cancer was associated with a positive IgG2 CagA response (OR = 3.74, 95% CI, 1.81 - 5.37) and with a low titer of total-IgG CagA antibodies (OR = 2.18, 95% CI, 1.35 - 2.69). Our results suggest that the IgG2 response to CagA might be used as a novel serologic marker to identify patients with H. pylori-associated gastric cancer.Journal of Medical Microbiology 01/2013; 62. DOI:10.1099/jmm.0.050567-0 · 2.27 Impact Factor
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ABSTRACT: Helicobacter pylori infection is a major cause of gastric cancer. Although identifying H. pylori infected subjects is the first approach for delineating the high-risk population for gastric cancer, the presence of H. pylori antibodies is not sufficient for gastric cancer screening. Among H. pylori infected subjects, only a minority of infected individuals develop gastric cancer. Serologic markers of H. pylori infection can serve as potential predictors for the development of gastric cancer. Serum or urinary H. pylori antibodies, cytotoxin-associated gene A antibodies, pepsinogen and microRNAs were reported to be associated with precancerous lesions or gastric cancer. In this review, we summarized the utilities and limitations of each strategy.Biomarkers in Medicine 10/2014; 8(9):1127-37. DOI:10.2217/bmm.14.72 · 2.86 Impact Factor
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ABSTRACT: The coexistence of two aetiologically distinct types of cardia cancer, with distinctive histological characteristics of the neoplastic and nonneoplastic gastric mucosa, may explain the heterogeneous evidence of its association with Helicobacter pylori infection. We compared gastric cardia and noncardia cancers with regard to the frequency of H. pylori infection, the histological characteristics of the nonneoplastic gastric mucosa and the tumour histological type. We evaluated 41 cardia and 339 noncardia cancer cases undergoing gastrectomy, and 380 community controls. H. pylori infection and CagA infection status were assessed by enzyme-linked immunosorbent assay and western blot, respectively. Histological characteristics of the neoplastic and nonneoplastic mucosa were obtained from pathology reports. The association between infection and cancers with different location was quantified in a case-control analysis and cardia and noncardia cancers were further compared. No positive relation was found for H. pylori infection, but CagA-positive strains were associated with an increased risk of noncardia cancer (odds ratio=1.60, 95% confidence interval=1.17-2.18). Twenty-seven (65.8%) cardia cancer cases, predominantly of the intestinal type (66.7%), had nonneoplastic atrophic mucosa and 208 (61.4%) noncardia cancers (56.7% of the intestinal type). Among the cases occurring in nonatrophic patients, the proportion of cancers of the Laurén's intestinal type was 71.4% for cardia and 54.2% for noncardia gastric cancers. Cardia and noncardia cancers were similar with regard to the relation with infection, histological type and condition of the nonneoplastic mucosa, supporting the predominance of cardia cancers determined by H. pylori infection in this European high-risk setting.European journal of cancer prevention: the official journal of the European Cancer Prevention Organisation (ECP) 03/2011; 20(2):96-101. DOI:10.1097/CEJ.0b013e3283429e77 · 2.76 Impact Factor