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: Helicobacter pylori infection is the most important risk factor for gastric cancer, but no association with cardia cancer has been recognized. However, a heterogeneous distribution of etiologically distinct types of cardia cancer may contribute to explain conflicting findings between studies in high- and low-risk settings. We aimed to quantify the association between H. pylori infection and gastric cardia cancer through meta-analysis, and to provide an explanation for the expected heterogeneity of results. We systematically reviewed published studies addressing the association between H. pylori infection and gastric cardia cancer (up to June 2009), and extracted relative risk (RR) estimates for the association with cardia and non-cardia cancers. Summary RR estimates and 95% confidence intervals (95% CI) were computed using random-effects models. Subgroup analyses were conducted, namely according to gastric cancer risk settings. Thirty-four articles were considered for meta-analysis. For cardia cancer, summary RR was 1.08 (95% CI 0.83-1.40; I (2) = 52.8%), higher in high-risk (RR = 1.98; 95% CI 1.38-2.83; I (2) = 18.4%) than in low-risk settings (RR = 0.78; 95% CI 0.63-0.97; I (2) = 11.6%). For non-cardia cancer, RR estimates were similar in high- (RR = 3.02; 95% CI 1.92-4.74; I (2) = 90.7%) and low-risk settings (RR = 2.56; 95% CI 1.99-3.29; I (2) = 46.6%). These observations were consistent across different inclusion criteria and when accounting for the virulence of the infecting strains. In high-risk settings, a positive association between H. pylori infection and gastric cancer was observed both for cardia and non-cardia cancers. The results support the hypothesis of a heterogeneous distribution of etiologically distinct types of cardia cancer.Cancer Causes and Control 03/2011; 22(3):375-87. · 3.20 Impact Factor
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ABSTRACT: Thirty years of research with animal models has shown that pancreatic adenocarcinoma is induced by N-nitrosamine carcinogens, which damage DNA through adduct formation. Human risk factors for pancreatic cancer include gastric colonization by Helicobacter pylori, as well as dietary intake of those same N-nitrosamines or of nitrite which forms those N-nitrosamines in the stomach, and cigarette smoking which also contains those N-nitrosamines. Physiologic actions of H. pylori colonization enhance the carcinogenic effect of N-nitrosamines delivered by smoking or dietary sources. This effect is modulated by host inflammatory response to the organism, by various virulence and other properties of the Helicobacter itself, and by host-organism interactions. A recent genome-wide association study identified SNPs within the ABO 9q34 locus as statistically significantly associated with risk of pancreatic cancer. A number of recent and older studies going back 40 yr also support the ABO association. ABO-product antigens are expressed on gastrointestinal epithelium on which H. pylori binds, and ABO genotype is known to be associated with risks of duodenal and gastric ulcer and with risk of gastric cancer, conditions definitively related to Helicobacter colonization. We suspect that ABO genotype/phenotype status influences the behavior of H. pylori which in turn affects gastric and pancreatic secretory function, and these ultimately influence the pancreatic carcinogenicity of dietary- and smoking-related N-nitrosamine exposures, and thus risk of pancreatic cancer. Our study results on the interaction of ABO and H. pylori significantly confirm this hypothesis and together with other existing studies strongly implicate this organism in the disease etiology.Molecular Carcinogenesis 01/2012; 51(1):109-18. · 4.27 Impact Factor
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ABSTRACT: For 63 years scientists in the Atomic Bomb Casualty Commission and its successor, the Radiation Effects Research Foundation, have been assessing the long-term health effects in the survivors of the atomic bombings of Hiroshima and Nagasaki and in their children. The identification and follow-up of a large population (approximately a total of 200,000, of whom more than 40% are alive today) that includes a broad range of ages and radiation exposure doses, and healthy representatives of both sexes; establishment of well-defined cohorts whose members have been studied longitudinally, including some with biennial health examinations and a high survivor-participation rate; and careful reconstructions of individual radiation doses have resulted in reliable excess relative risk estimates for radiation-related health effects, including cancer and noncancer effects in humans, for the benefit of the survivors and for all humankind. This article reviews those risk estimates and summarizes what has been learned from this historic and unique study.Disaster Medicine and Public Health Preparedness 03/2011; 5 Suppl 1:S122-33. · 1.14 Impact Factor