Helicobacter pylori Infection and Risk of Gastric Cancer in Shanghai, China: Updated Results Based upon a Locally Developed and Validated Assay and Further Follow-Up of the Cohort

Department of Preventive Medicine, University of Southern California/Norris Comprehensive Cancer Center, University of Southern California School of Medicine, Los Angeles 90033-0800, USA.
Cancer Epidemiology Biomarkers & Prevention (Impact Factor: 4.13). 08/1999; 8(7):621-4.
Source: PubMed


Infection with Helicobacter pylori has been associated with an increased risk of gastric cancer in low-risk populations. However, our previous results (P. M. Webb et al., Int. J. Cancer, 67: 603-607, 1996) from an ongoing prospective study in Shanghai, China, a relatively high-risk population, failed to show an association between H. pylori infection and the subsequent risk of gastric cancer. That previous study had a relatively short time period of follow-up and the enzyme-linked immunosorbent assay (ELISA) used was based on strains found in Southern England and without validation among the Chinese. Either one of these two factors could have had an impact on the validity of those earlier observations. An ELISA developed and validated among Shanghai residents was used in the present study to reexamine specific antibodies to H. pylori in 188 gastric cancer patients and 548 control subjects. All of the cases of gastric cancer were identified during the first 12 years of follow-up of a cohort of 18,244 men, ages 45-64 years in Shanghai, from whom blood samples were collected at enrollment during 1986-1989. For each cancer case, three cancer-free control subjects were randomly selected from the cohort and matched to the index cases by age (within 2 years), month and year of sample collection, and neighborhood of residence. The Shanghai-based ELISA detected a higher prevalence of serum antibodies to H. pylori than the English-based assay in both gastric cancer cases (86 versus 53%) and control subjects (85 versus 56%). Virtually all of the subjects (98%) who were H. pylori-seropositive by the English-based assay tested positive by the Shanghai-based assay. On the other hand, 73% of gastric cancer cases and 68% of control subjects who were seronegative according to the English-based assay tested positive by the Shanghai-based assay. Using this alternative assay, combined with increased follow-up, our latest data contradict our earlier findings and show a statistically significant association between H. pylori seropositivity and gastric cancer risk (odds ratio, 1.84; 95% confidence interval, 1.08-3.11). We noted an increasing rate of seropositivity among cases as the time interval between cohort enrollment and cancer diagnosis increased. Among subjects followed for 5 or more years after enrollment, the odds ratio for gastric cancer related to H. pylori seropositivity was 3.74 (95% confidence interval, 1.51-9.30).

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    • "This positive association was also observed in two prospective cohort studies. Yuan et al. [34] reported that the odds ratio was 3.74 for individuals who were seropositive for H. pylori and followed for 5 or more years in a nested case-control study with a cohort of Shanghai residents. A prospective, nested case-control study in Linxian, one of the highest-incidence regions in China, found that H. pylori seropositivity was associated with an approximately two-fold increased risk of gastric cancer [35]. "
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    ABSTRACT: Background Gastric cancer is one of the most common and lethal malignant cancers worldwide, and numerous epidemiological studies have demonstrated that Helicobacter pylori (H. pylori) infection plays a key role in the development of gastric carcinomas. Our previous studies showed that aquaporin 3 (AQP3) is overexpressed in gastric carcinoma and promotes the migration and proliferation of human gastric carcinoma cells, suggesting that AQP3 may be a potentially important determinant of gastric carcinoma. However, the role of AQP3 in H. pylori carcinogenesis is unknown. Methods The AQP3 protein and H. pylori were detected in human gastric tissues by immunohistochemistry and modified Giemsa staining respectively. AQP3 knockdown was obtained by small interfering (si) RNA. Western blot assays and RT-PCR were used to evaluate the change of AQP3 in the human gastric cancer AGS and SGC7901 cell lines after co-culture with H. pylori. Sprague Dawley rats were orally inoculated with H. pylori to establish a rat model colonized by H. pylori. Results The present study found that AQP3 expression correlated with H. pylori infection status in gastric cancer tissues and corresponding normal mucosa, and H. pylori co-culture upregulated AQP3 expression in human gastric adenocarcinoma cells in vitro via the extracellular signal-regulated kinase signaling pathway. H. pylori infection also increased AQP3 expression in gastric mucosa colonized by H. pylori in a Sprague Dawley rat model. Conclusions These findings provide further information to understand the mechanism of H. pylori carcinogenesis and a potential strategy for the treatment of H. pylori-associated gastric carcinoma.
    PLoS ONE 11/2012; 7(11):e49104. DOI:10.1371/journal.pone.0049104 · 3.23 Impact Factor
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    • "H. pylori is an established cause of gastric cancer, but some studies from China have shown a lower relative risk of gastric cancer associated with this bacterium compared with results reported from Western countries (Yuan et al, 1999; Kamangar et al, 2006a). The direction and magnitude of the association we observed is consistent with previous studies from China (Yuan et al, 1999). The lack of significance is perhaps because few people were negative for H. pylori and consequently there was low power to detect an association. "
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    ABSTRACT: Circulating pepsinogens can indicate atrophic gastritis, a precursor of gastric cancer. We tested the association between gastric cancer and plasma pepsinogens and antibodies against Helicobacter pylori in a case-control study nested in a prospective cohort. We selected 141 gastric cancer cases and 282 incidence-density sampled controls. Plasma concentrations of pepsinogens 1 and 2 were measured using ELISA kits, and anti-H. pylori antibodies were measured using a kit specific to Chinese strains. Associations were estimated using conditional logistic regression models adjusted for potential confounders. Gastric cancer subjects were more likely to be anti-H. pylori positive than controls, 97 vs 92%. A plasma pepsinogen 1 (PG1) concentration <50 ng ml(-1) (15% of cases) was associated with a significantly increased risk of gastric cancer (OR 4.23; (95% CI: 1.86-9.63), whereas a plasma pepsinogen 2 (PG2) concentration >6.6 ng ml(-1) (75% of cases) was also associated with a significantly increased risk of gastric cancer (OR 3.62; (95% CI: 1.85-7.09). We also found that the PG1 : 2 ratio had a nearly linear association with gastric cancer risk. Lower plasma PG1 : 2 ratios are associated with a higher risk of gastric cancer. Furthermore, it appears that circulating pepsinogens 1 and 2 may be independently associated with the risk of gastric cancer.
    British Journal of Cancer 03/2011; 104(9):1511-6. DOI:10.1038/bjc.2011.77 · 4.84 Impact Factor
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    • "Overall (I-squared = 84.4%, p = 0.000) High-risk settings Talley, 1991 Kato, 2004 Mitchell, 2008 Lee, 1998 ID Yuan, 1999 "
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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. DOI:10.1007/s10552-010-9707-2 · 2.74 Impact Factor
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