Low-Positive Antibody Titer againstHelicobacter pyloriCytotoxin-Associated Gene A (CagA) May Predict Future Gastric Cancer Better Than Simple Seropositivity againstH. pyloriCagA or againstH. pylori

Suzuki, Gen; Cullings, Harry M.; Fujiwara, Saeko; Hattori, Nobuyuki; Matsuura, Shinsuke; Hakoda, Masayuki; Akahoshi, Masazumi; Kodama, Kazunori; Tahara, Eiichi

doi:10.1158/1055-9965.epi-06-1048

Cited by 35 publications

(42 citation statements)

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“…1. After a systematic databases search and manual review of reference lists in eligible studies, a total of 12 publications on the diagnostic accuracy of anti-CagA antibody in GC patients were considered eligible for inclusion in present study [19][20][21][22][23][24][25][26][27][28][29][30]. Studies were excluded for primarily the following considerations: they were not diagnostic studies, they did not report sufficient data to construct a 2×2 table, they used the same case series or overlapping case series, or they mixed other cancer types.…”

Section: Literature Search and Study Design Characteristicsmentioning

confidence: 99%

Serum Helicobacter pylori CagA antibody may not be used as a tumor marker for diagnosing gastric cancer in east Asian countries

Zhao

Li²,

Liu

et al. 2014

Tumor Biol.

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Gastric cancer (GC) is a highly malignant cancer with increasing incidence and mortality worldwide. Serum Helicobacter pylori CagA antibody has been widely reported to play an important role in diagnosing GC. However, published data on this subject are inconclusive. Therefore, we performed a meta-analysis to evaluate the sensitivity and specificity of serum H. pylori CagA antibody in the diagnosis of GC. We conducted a comprehensive search to identify eligible related studies, in which the pooled sensitivity, specificity, diagnostic odds ratio (DOR), and summary receiver operating characteristic (SROC) curves could be determined. A total of 12 studies including 1,524 cases and 3,324 controls who fulfilled all of the inclusion criteria were included for analysis. The summary estimates for serum H. pylori CagA antibody in the diagnosis of GC in these studies were pooled sensitivity 0.71 (95 % CI 0.69-0.73), specificity 0.40 (95 % CI 0.39-0.42), DOR 2.11 (95 % CI 1.55-2.8), and the area under the curve was 0.636. Our meta-analysis showed that serum H. pylori CagA antibody should not be used for detecting GC.

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Section: Literature Search and Study Design Characteristicsmentioning

confidence: 99%

Serum Helicobacter pylori CagA antibody may not be used as a tumor marker for diagnosing gastric cancer in east Asian countries

Zhao

Li²,

Liu

et al. 2014

Tumor Biol.

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“…The evidence supporting this lack of association, however, is based on contradictory findings (Dawsey et al, 2002;Huang et al, 1998Huang et al, , 2003. Studies from Western countries support a negative association between H. pylori infection and cardia cancer (Enroth et al, 2002;Brenner et al, 2004;Kato et al, 2004;Nomura et al, 2005;Shin et al, 2005;Kamangar et al, 2006;Knekt et al, 2006), whereas there is a trend towards positive association in studies from Eastern Asia (Kato et al, 2004;Shin et al, 2005;Yang et al, 2006;Kamangar et al, 2007;Suzuki et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

Is cardia cancer aetiologically different from distal stomach cancer?

Peleteiro

Pinto

Barros

et al. 2011

European Journal of Cancer Prevention

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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.

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“…pylori to colonize, causing fading of the IgG response (Nomura et al, 2002;Suzuki et al, 2007). However, little is known about changes in the response of IgG subclasses to H. pylori antigens during disease progression.…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, there also exists evidence that both age and the severity of the mucosal lesions negatively influence the performance of CagA as a serological marker for GC (Camorlinga-Ponce et al, 2008). An association between the presence of GC and a low titre of anti-CagA antibodies has also been reported (Nomura et al, 2002;Suzuki et al, 2007). These heterogeneous results make it difficult to use simple CagA-positive serology as a marker for malignancy.…”

Section: Introductionmentioning

confidence: 99%

IgG2 response and low IgG titre specific to Helicobacter pylori CagA as serological markers for gastric cancer

Cruz-Herrera

Flores-Luna

Gutiérrez‐Xicoténcatl

et al. 2013

Journal of Medical Microbiology

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Infection with Helicobacter pylori cytotoxin-associated gene A (CagA)-positive strains is associated with the development of gastric cancer (GC). However, some reports have failed to demonstrate an increased frequency of CagA antibodies in GC patients. This study evaluated the response of IgG antibody and subclasses IgG1 and IgG2 against both CagA and H. pylori membrane antigens in patients with pre-cancerous lesions and cases with GC. A total of 137 patients with a positive serum IgG response to H. pylori were selected: 46 with intestinal metaplasia, 41 with gastric adenocarcinoma and 50 with non-atrophic gastritis (NAG) 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 with NAG patients, GC patients showed a higher frequency of IgG2 CagA antibodies (55.2 vs 15.4 %, P50.001), but a lower frequency (80.5 vs 96.0 %, P50.021) and diminished levels of IgG2 H. pylori antibodies [12.5 vs 21.9 ELISA units (EU), P50.007]. GC patients also presented lower levels of CagA (32.6 vs 42.4 EU, P50.004) and H. pylori total IgG (33.7 vs 38.7 EU, P50.029). GC was associated with a positive IgG2 CagA response [odds ratio (OR)53.74, 95 % confidence interval (CI) 1.81-5.37; P50.002] and with a low titre of total IgG CagA antibodies (OR52.18, 95 % CI 1.35-2.69; P50.006). These results suggest that the IgG2 response to CagA could be used as a novel serological marker to identify patients with H. pylori-associated GC. INTRODUCTIONAccording to estimations based on seroprevalence studies, half of the world population is infected with Helicobacter pylori (Brown, 2000). In 1994, the International Agency for Research on Cancer classified H. pylori as a class 1 human carcinogen (IARC Working Group, 1994). As reported by meta-analyses, a two-to threefold increased risk of stomach cancer is associated with this infection (Huang et al., 1998;Eslick et al., 1999). Gastric malignancy is the fourth most common type of cancer and the second most common cause of cancer-related deaths worldwide (Parkin et al., 2005). H. pylori infection induces a chronic inflammation of the gastric mucosa that is intensified by high levels of proinflammatory cytokines during the immune response, especially in the case of strains possessing the cagA gene (Peek et al., 1995; Yamaoka et al., 1997). In a small proportion of infected individuals and over a decades-long process, this chronic inflammation leads to the development of gastric cancer (GC) through a series of progressive stages that include non-atrophic gastritis (NAG), atrophic gastritis, metaplasia and dysplasia (Correa, 1996).The cagA gene of H. pylori is located in the cag pathogenicity island (cag-PAI). The CagA toxin is injected into the gastric Abbreviations: cagA, cytotoxin-associated gene A; cag-PAI, cag pathogenicity island; CI, confidence interval; DC, dendritic cell; EU, ELISA units;...

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Low-Positive Antibody Titer againstHelicobacter pyloriCytotoxin-Associated Gene A (CagA) May Predict Future Gastric Cancer Better Than Simple Seropositivity againstH. pyloriCagA or againstH. pylori

Cited by 35 publications

References 30 publications

Serum Helicobacter pylori CagA antibody may not be used as a tumor marker for diagnosing gastric cancer in east Asian countries

Serum Helicobacter pylori CagA antibody may not be used as a tumor marker for diagnosing gastric cancer in east Asian countries

Is cardia cancer aetiologically different from distal stomach cancer?

IgG2 response and low IgG titre specific to Helicobacter pylori CagA as serological markers for gastric cancer

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