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  • Original Article
  • OPEN ACCESS

Helicobacter pylori Infection and Risk of Cardia Gastric Cancer in Asian Countries: A Systematic Review and Meta-analysis

  • Yinnan Zhu1,
  • Yuan Ding1,
  • Qiliu Qian1,
  • Wanyue Zhang1,
  • Qingxia Wang1 and
  • Ruihua Shi2,* 
 Author information
Cancer Screening and Prevention   2024;3(3):142-153

doi: 10.14218/CSP.2024.00016

Abstract

Background and objectives

The incidence of cardia gastric cancer (CGC) is rising worldwide, particularly in East Asia. There has been a debate over whether Helicobacter pylori (H. pylori) constitutes a risk factor for CGC. This study aimed to evaluate the relative risk of H. pylori infection and CGC in Asian countries.

Methods

Relevant studies examining H. pylori and CGC were searched in PubMed, Embase, and Web of Science from their inception to June 30, 2024. Either a random-effect model or a fixed-effect model was used to calculate pooled odds ratios (ORs) with 95% confidence intervals (CIs). Sensitivity analyses and assessments of publication bias were performed. The stability of results was evaluated in cases where publication bias was detected.

Results

A total of 24 studies were included in the meta-analysis. A significant association between H. pylori and CGC was observed (OR = 2.20, 95% CI 1.73–2.80). In a subgroup analysis of different countries, a significant association was observed in East Asian countries, including China (OR = 2.12, 95% CI 1.63–2.77), Japan (OR = 2.21, 95% CI 1.16–4.20), and Korea (OR = 2.36, 95% CI 1.58–3.54), but not in Iran (OR = 1.48, 95% CI 0.77–2.84). The pooled OR from five prospective cohort studies revealed a strong association between H. pylori and CGC (OR = 2.32, 95% CI 1.47–3.66).

Conclusions

East Asia bears a significant burden of H. pylori-related CGC. A clear association between H. pylori infection and CGC was observed in this region.

Keywords

Cardia gastric cancer, Helicobacter pylori, Risk factor, East Asia, Meta-analysis, Systematic review

Introduction

According to statistical sources, there were more than 960,000 new cases of gastric cancer worldwide in 2022, with about 660,000 fatalities. Gastric cancer is the fifth most prevalent malignancy and the fifth leading cause of cancer-related death globally. It can be divided into two subsites based on anatomical location: cardia gastric cancer (CGC) and non-cardia gastric cancer (NCGC).1 East Asia has the highest incidence of CGC in the world, and the incidence continues to show an upward trend.2

East Asia has a 54.1% overall Helicobacter pylori (H. pylori) infection rate, which is significantly higher than that of other regions. Furthermore, this region bears a high burden of gastric cancer related to H. pylori infection.3 Several studies have identified a substantial connection between H. pylori infection and NCGC.4 Correa described the progression from H. pylori infection, chronic gastritis, chronic atrophic gastritis, intestinal metaplasia, and atypical hyperplasia to cancer, a pathway widely recognized in NCGC.5 Additionally, H. pylori eradication therapy has been shown to reduce the incidence of gastric cancer and related mortality.6 However, the relationship between H. pylori and CGC has remained controversial due to the unique anatomical position of CGC. A previous meta-analysis found a positive correlation in East Asia (odds ratio (OR) = 2.9, 95% confidence interval (CI) 2.3–2.6) and a negative correlation in the West (OR = 0.8, 95% CI 0.6–1.0).4 A recent multicenter prospective case-control study of 500,000 Chinese individuals found that at least 78% of NCGC and 62% of CGC can be attributed to H. pylori.7 However, the latest meta-analysis included studies on duplicate populations, which may have affected the results.4 Therefore, our goal was to more convincingly evaluate the relative risk of H. pylori infection and CGC in Asian populations.

Materials and methods

Search strategy

This systematic review and meta-analysis, registered in PROSPERO (CRD42023432339), was conducted in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) 2020 statement.8 All relevant studies were retrieved from three databases, including PubMed, Embase, and Web of Science, from their inception up to June 30, 2024. The following search terms were utilized: (“cardia” OR “proximal” OR “esophagogastric junction” OR “gastroesophageal junction”) AND (“neoplasm” OR “tumor” OR “cancer” OR “neoplasia” OR “carcinoma” OR “adenocarcinoma”) AND (“helicobacter pylori” OR “helicobacter nemestrinae” OR “campylobacter pylori” OR “H. pylori”). The detailed search strategy is provided in Table S1. Additionally, reference lists of relevant studies were checked to identify additional eligible studies. Two collaborators independently retrieved and evaluated the included studies, with disagreements resolved through consensus.

Inclusion and exclusion

All studies investigating the association between H. pylori infection and CGC in Asian populations were considered for screening. H. pylori detection methods included histology, rapid urease testing, culture, serology, or carbon-urea breath testing. The inclusion criteria were carefully defined: (1) the study type included case-control, cross-sectional, or cohort studies; (2) the exposure variable was H. pylori infection; (3) the case group involved CGC, and the control group was free of gastric cancer; (4) the population was from Asian countries; (5) studies provided sufficient data to estimate ORs or risk ratios; and (6) studies were published in English with full text available. We attempted to exclude other types of gastroesophageal junction carcinoma, such as distal esophageal adenocarcinoma. Case reports, letters, comments, reviews, and duplicate publications were excluded.

Data extraction

Two authors extracted detailed information from each included study, including the first author, publication year, country, patient characteristics (age, sex), study design (study type, follow-up time, method of H. pylori detection), definition of CGC, and details of the case and control groups (sample size, H. pylori infection status, outcomes).

Quality assessment and risk of bias

The methodological quality of eligible studies was independently assessed by two authors using the Newcastle-Ottawa Scale for case-control and cohort studies. Studies with scores ranging from seven to nine points were considered high quality. The risk of bias was assessed using ROBINS-E, a tool for non-randomized exposure studies, across several domains, including confounding, participant selection, exposure measurement, post-exposure interventions, missing data, outcome measurement, and selection of reported results.9 A study was considered to have a high risk of bias if bias was present in at least one of the seven domains.

Statistical analysis

Pooled ORs with 95% CIs were calculated to assess the association between H. pylori and CGC. The model used was based on heterogeneity results, which were analyzed using the chi-squared (χ2) test (Cochran’s Q) and the inconsistency index (I2). A random-effect model was employed when significant heterogeneity was identified (χ2P < 0.05 or I2 > 50%); otherwise, a fixed-effect model was applied. The aim of our analysis was to investigate the association between H. pylori infection and the risk of CGC. Subgroup analyses were conducted to explore effect modification based on study-level factors such as country, detection time of H. pylori, publication year, and duration of follow-up. Sensitivity analyses were performed to explore potential sources of heterogeneity. Publication bias was evaluated using funnel plots (Begg’s and Egger’s regression tests). All analyses were performed using Review Manager V.5.4 and STATA 15, with statistical significance defined as P < 0.05.

Results

Literature search and study characteristics

The PRISMA flowchart is presented in Figure 1. The preliminary literature search yielded a total of 4,308 articles from PubMed, Embase, and Web of Science. After removing 1,829 duplicates and excluding 2,393 unrelated articles based on title and abstract screening, 86 studies remained for full-text review. Finally, 24 full-text articles were included in the final analysis,7,10–32 after excluding six studies that used duplicate populations.33–38 The analysis involved 2,529 CGC cases and 52,556 control subjects. The study populations of the 24 included studies were from Asian countries (eight in China, nine in Japan, five in Korea, and two in Iran). The characteristics and quality scores of the eligible articles are shown in Table 1. Using the ROBINS-E risk of bias tool, three studies were rated as high risk of bias, six as moderate risk, and the remainder as low risk (Fig. 2).

Flowchart of the systematic search and selection process.
Fig. 1  Flowchart of the systematic search and selection process.
Table 1

Characteristics of 24 studies

First authorYearCountryDesignStudy periodMedian follow-up (year)H.pylori methodAge (year)Male (%)Number of CGC/controlDefinition of CGCNOS
Chen102009Taiwan, Chinacase-control2000–2009–ELISACGC: 64.53 ± 2.17 Control: 63.27 ± 1.73100
100		41/205within 5mm to GEJ8
Cho112010Koreacase-control2003.6–2007.4–ELISACase: 58.1 ± 12.0
Control: 53.0 ± 7.0		68.8
50.0		216/562within 2cm distal to GEJ8
Derakhshan122008Irancase-control––ELISACGC: 63.8 ± 7.1
Control:matched		69.8
–		53/53within 2cm distal to GEJ7
Gao132022Chinacase-control2010–2014–ImmunoblotCGC: 69.3 ± 7.9
Control: 66.3 ± 8.71		67.9
69.1		349/1,859within 5cm to GEJ8
Horii142011Japancase-control2000.8–2009.1–histology/RUT/ELISACGC: 68.7 ± 9.5
Control: 61.7 ± 8.3		87.0
93.5		23/46within 2cm to GEJ8
Inoue152020Japancohort1993–199418ELISA56.7 ± 8.3Case: 62.2
Control: 37.7		50/1,8511anatomical position7
Kamangar162007Chinacase-cohort1985–200110ELISACGC: 55.5 ± 7.7
Control: 51.9 ± 8.9		60.3
45.3		582/992proximal 3cm of the stomach8
Kato172004Japancase-control––ELISA––86/6,578–7
Kikuchi181995Japancase-control1988–1992–ELISAGC: 20–40
Control: 15–44		45.7
43.6		35/203–7
Kikuchi192000Japancase-control1993.6–1995.7–ELISAmatchedGC: 66.1
Control: 51.3		186/1,007upper third of stomach7
Kim201997Koreacase-control1994–histology/RUTGC: 57.3
Control: 56.9		65
61.9		12/160anatomical position6
Kim212012Koreacase-control2003.6–2011.2–histology/RUT/ELISA/tissue cultureCase: 60.3 ± 12.3
Control: 55.9 ± 11.9		67.3
33.7		60/270within 2cm below GEJ8
Komoto221998Japancase-control1991–1996–ELISAGC: 64.9 ± 1.2
Control: 62.4 ± 1.1		78.10
matched		14/105within 20mm distal to GEJ8
Lee231998Koreacase-control1992–1995–RUTGC: 54.4
Control: 40.5		67.4
71.7		17/113anatomical position7
Shakeri242015Irancase-control2004.12–2011.12–ELISA,multiplex serologyCGC: 66.3 ± 11.1
Mcontrol: 64.5 ± 9.1		78.2
77.2		142/276-8
Shibata251996Japancase-control––histologyGC: 62
Control: 61.8		74
74		5/50upper third of stomach6
Shin262005Koreanested case-control1993–19992.6ELISACases: 63.0
Control:matched		66
matched		6/24–8
Suzuki272007Japannested case-control1970.1–2001.122ELISACGC: 70 ± 11
Control: –		54.5
58.9		22/1,042–7
Wu282009Taiwan, Chinacase-control2000–2007–ELISAGC: 63.2 ± 13.5
Control: 40.2 ± 6.2		62.8
51.6		29/395within 3cm distal to GEJ8
Xie292020Chinacross-sectional2014.1–2016.6–13CCGC: 62.65 ± 5.27
Control: 53.30 ± 7.94		41.96
60.87		23/1,225–8
Yamaoka301999Japancase-control––ELISAGC: 64.5
Control: matched		72.7
matched		23/23cardia and fundus6
Yan322024Chinacase-cohort2015–20176.313C54.741.876/18,233–8
Yang72021Chinacase-cohort2004.6–2008.710.1ImmunoblotCGC: 61.2 ± 8.6
Control: 59.1 ± 9.9		75.0
69.0		436/500–8
Yuan311999Chinacase-cohort1986–19895.2ELISAGC: 63.4 ± 5.6
Control: matched		–43/124–8

CGC, cardia gastric cancer; ELISA, enzyme linked immunosorbent assay; GC, gastric cancer; GEJ, gastroesophageal junction; NOS, Newcastle-Ottawa Scale; RUT, rapid urease test.

Assessment of risk of bias using the ROBINS-E.
Fig. 2  Assessment of risk of bias using the ROBINS-E.

Pooled data

The pooled OR for the association between H. pylori and CGC in Asian countries was 2.20 (95% CI 1.73–2.80), with significant heterogeneity (I2 = 66%, P < 0.001), based on a random-effect model (Fig. 3).

Forest plot for <italic>Helicobacter pylori</italic> infection among cardia gastric cancer.
Fig. 3  Forest plot for Helicobacter pylori infection among cardia gastric cancer.

CI, confidence interval; IV, inverse variance.

Subgroup analysis

Stratification by country

The included studies were from Asian countries. A significant association between H. pylori and CGC was observed in East Asian countries, including China (OR = 2.12 [95% CI 1.63–2.77], I2 = 58%, P < 0.001), Japan (OR = 2.21 [95% CI 1.16–4.20], I2 = 78%, P = 0.02), and Korea (OR = 2.36 [95% CI 1.58–3.54], I2 = 15%, P < 0.01), but not in Iran (OR = 1.48 [95% CI 0.77–2.84], I2 = 0%, P = 0.24) (Fig. 4a).

Subgroup analysis (a) by countries; (b) by detection time of <italic>Helicobacter pylori</italic>.
Fig. 4  Subgroup analysis (a) by countries; (b) by detection time of Helicobacter pylori.

CGC, cardia gastric cancer; CI, confidence interval; IV, inverse variance.

Stratification by detection time of H. pylori

It is possible that H. pylori infection could be cleared as the cancer progresses.39,40 Identifying the status of H. pylori before malignancy develops can help reduce false-negative results to some extent. Seven articles, including five cohort studies and two nested case-control studies, detected the status of H. pylori before the onset of CGC. A comparable correlation was observed regardless of H. pylori detection time (OR = 2.03 [95% CI 1.32–3.12], I2 = 69%, P = 0.001; OR = 2.27 [95% CI 1.67–3.09], I2 = 66%, P < 0.001) (Fig. 4b).

Stratification by publication time

Between 1990–2000 and 2000–2010, there was a significant association between H. pylori and CGC (OR = 2.83 [95% CI 1.55–5.19], I2 = 58%, P < 0.001; OR = 2.10 [95% CI 1.55–2.86], I2 = 48%, P < 0.001). However, the pooled studies published from 2010 to 2020 showed no correlation (OR = 1.56 [95% CI 0.73–3.32], I2 = 72%, P = 0.25) (Fig. 5a).

Subgroup analysis (a) by publication time; (b) by duration of follow-up time.
Fig. 5  Subgroup analysis (a) by publication time; (b) by duration of follow-up time.

CGC, cardia gastric cancer; CI, confidence interval; IV, inverse variance.

Stratification by follow-up time

Seven of the studies were retrospective or prospective cohort studies, with five being prospective studies with a follow-up period of more than five years. The pooled data analysis of five studies revealed a notable association between H. pylori and CGC (OR = 2.32 [95% CI 1.47–3.66], I2 = 75%, P < 0.001), while no correlation was seen in two studies with follow-ups of less than five years (OR = 0.94 [95% CI 0.36–2.46], I2 = 0%, P = 0.90) (Fig. 5b).

Publication bias and sensitivity analysis

Publication bias was evaluated using Begg’s and Egger’s tests. No substantial publication bias was observed (P-value of Begg’s test = 0.980, P-value of Egger’s test = 0.503) (Fig. S1). Furthermore, visual inspection of the funnel plot shapes revealed no significant evidence of asymmetry among the studies (Fig. 6). The study by Kikuchi et al.19 deviated from the line of symmetry, which could be attributed to the study population being primarily composed of patients under the age of 40. We assessed the contribution of each study to the overall pooled OR through a leave-one-out sensitivity analysis. The stability of the results was confirmed, as no single study significantly influenced the pooled OR (Fig. 7). When combined with the results of the subgroup analysis, the heterogeneity was attributed to various factors, including differences in the definition of CGC, study population, and H. pylori detection methods.

Funnel plot.
Fig. 6  Funnel plot.

OR, odds ratio.

Sensitivity analysis.
Fig. 7  Sensitivity analysis.

CI, confidence interval.

Discussion

The incidence rate of CGC is increasing in Asian countries. The proportion of CGC in Japan has risen from 2.3% to 10.0% in recent years.41 In high-incidence areas of China, the rate can reach 50/100,000.42 The risk factors and etiology of CGC are debatable but appear to be related to geography and ethnicity. Previous studies have yielded contradictory conclusions about the relationship between H. pylori and CGC.4,43–46 Han et al.4 conducted a meta-analysis that demonstrated a significant association between H. pylori infection and CGC in East Asia, but the analysis included studies using duplicated populations. Moreover, the most recent meta-analysis by Gu et al.47 completed the literature search in December 2021. Recent papers could significantly affect these conclusions. Therefore, we updated the literature and excluded studies using duplicated populations to analyze any new associations between H. pylori and CGC in Asia.

A total of 24 studies were included in our meta-analysis. The H. pylori infection rate in CGC cases was 2.20 times greater than that in the control group, confirming that H. pylori is a clear risk factor for CGC. At the same time, we conducted a subgroup analysis for different countries. The outcomes revealed that infected individuals from East Asia (China, Japan, and Korea) had a twofold higher risk of developing CGC than the control group, whereas no correlation was found in Iran. Our analysis only included two Western Asia-related studies from Iran. Western Asia has much lower age-standardized incidence rates of stomach and esophageal malignancies than Eastern Asia, which ranks first.48 Additionally, several previous studies confirmed a null or negative correlation between H. pylori and CGC in Western populations or low-incidence regions.4,43,44,46 Hence, a positive association between H. pylori and CGC was only observed in East Asia.

Because of the unique location of the esophagogastric junction (GEJ), CGC is likely a heterogeneous tumor originating from different mucosal types. Internationally, various definitions and classification standards exist. The Siewert classification, proposed in 1987 and extensively used, refers to adenocarcinomas located within 5 cm of the GEJ, including type I (located 1 to 5 cm above the GEJ), type II (located 1 cm above to 2 cm below the GEJ), and type III (located 2 to 5 cm below the GEJ).49 The Kyoto International Consensus Report in 2022 stated that adenocarcinomas within 1 cm of the GEJ should be classified as “cardia cancer”.50 Several studies have found geographical variations in the pathogenesis of CGC. In the West, it is often associated with excessive gastric acid damage caused by gastroesophageal reflux disease, similar to esophageal adenocarcinoma. In East Asia, CGC is associated with gastric mucosal atrophy induced by H. pylori infection, similar to distal gastric cancer.12,51,52 Urabe et al.53 demonstrated that gastric cancers and type III adenocarcinoma of the esophagogastric junction had a similar background mucosal type. Based on survey data from three high-incidence areas in China, the long-term morbidity and mortality risk of CGC increased as the severity of cardia mucosal lesions increased. Trend analysis revealed a positive correlation between the degree of mucosal lesions and the H. pylori infection rate.54 To summarize, severe mucosal atrophy and intestinal metaplasia increase the risk of CGC to some extent. The question of whether its occurrence and development follow the path of Correa needs further exploration. Additionally, the strain type of H. pylori and host susceptibility also play roles in the complex process of carcinogenesis. Current clinical research has found that compared to NCGC, CGC tends to present at a later pTNM stage and has worse clinical outcomes.55 Therefore, identifying risk factors, performing early screening, and implementing interventions are critical in clinical practice.

In addition, the accuracy of H. pylori status is affected by various factors. The first issue involves methodological limitations. In one prospective study, the relationship between H. pylori and the risk of NCGC assessed by immunoblot was more than threefold higher than that assessed by ELISA (enzyme linked immunosorbent assay),56 indicating that detection techniques have different sensitivity levels. Secondly, anti-H. pylori therapy for atrophic gastritis prior to malignancy should be considered. Moreover, both histological infection and serological antibody titers of H. pylori may be cleared or decreased as cancer progresses.39 As a result, the H. pylori infection rate may be underestimated due to the factors described above. We performed a subgroup analysis based on the detection time of H. pylori and found that there was a consistent correlation regardless of detection time, and heterogeneity was not primarily due to this factor. The results from five prospective cohort studies appear to be more reliable. We did not conduct a subgroup analysis of different detection methods because only a few studies employed the immunoblot method.

This meta-analysis has certain limitations. First, although we performed sensitivity analysis to evaluate the stability of the results, the source of heterogeneity remains somewhat difficult to explain. At least half of the studies contributed to the heterogeneity. On the one hand, the criteria for CGC in various studies have not been standardized, resulting in heterogeneity in study populations. Second, various methods were used to detect H. pylori. Studies focusing on younger patients may also have contributed to the heterogeneity. Third, the majority of the included studies were retrospective case-control studies, which are subject to selection bias and confounding variables. Although most studies were matched by age and gender, other risk factors, including diet, smoking, alcohol consumption, gastroesophageal reflux disease, and gastrointestinal ulcers, may confound the relationship between H. pylori and CGC.57 Additional adjustments are required for these risk variables. Furthermore, our conclusions primarily focus on East Asian populations due to the lack of sufficient information from countries outside East Asia. Despite the constraints of our study, we updated the latest relevant literature. In addition, we identified and excluded studies using duplicate population cohorts, compared to a prior meta-analysis.4 In summary, H. pylori infection is a risk factor for CGC in East Asia. It is meaningful to conduct early detection and intervention.

Conclusions

East Asia bears a significant burden of CGC, where a positive association between H. pylori infection and CGC has been observed. We anticipate the development of more reliable endoscopic techniques and pathology diagnostics to better identify the origin of cancer in the gastroesophageal junction area. Additionally, more valuable prospective cohort studies and randomized controlled trials are needed. Identification of risk factors and early intervention are critical for reducing the incidence of CGC.

Supporting information

Supplementary material for this article is available at https://doi.org/10.14218/CSP.2024.00016 .

Table S1

Detailed search strategy in three databases.

(DOCX)

Click here for additional data file.

Fig. S1

Begg’s and Egger’s regression tests.

(TIF)

Click here for additional data file.

Declarations

Acknowledgement

None.

Data sharing statement

The datasets used in support of the findings of this study are available from the corresponding author at [email protected] upon request.

Funding

None.

Conflict of interest

One of the authors, Prof. Ruihua Shi has been an associate editor of Cancer Screening and Prevention since March 2022. There are no other conflicts of interest regarding the publication of this paper.

Authors’ contributions

Material preparation, data collection, and analysis (YNZ, YD), writing of the first draft of the manuscript (YNZ). All authors contributed to the study’s conception and design and commented on previous versions of the manuscript. All authors read and approved the final manuscript.

References

  1. Arnold M, Ferlay J, van Berge Henegouwen MI, Soerjomataram I. Global burden of oesophageal and gastric cancer by histology and subsite in 2018. Gut 2020;69(9):1564-1571 View Article PubMed/NCBI
  2. Huang J, Lucero-Prisno DE, Zhang L, Xu W, Wong SH, Ng SC, et al. Updated epidemiology of gastrointestinal cancers in East Asia. Nat Rev Gastroenterol Hepatol 2023;20(5):271-287 View Article PubMed/NCBI
  3. de Martel C, Georges D, Bray F, Ferlay J, Clifford GM. Global burden of cancer attributable to infections in 2018: a worldwide incidence analysis. Lancet Glob Health 2020;8(2):e180-e190 View Article PubMed/NCBI
  4. Han Z, Liu J, Zhang W, Kong Q, Wan M, Lin M, et al. Cardia and non-cardia gastric cancer risk associated with Helicobacter pylori in East Asia and the West: A systematic review, meta-analysis, and estimation of population attributable fraction. Helicobacter 2023;28(2):e12950 View Article PubMed/NCBI
  5. Correa P. Human gastric carcinogenesis: a multistep and multifactorial process—First American Cancer Society Award Lecture on Cancer Epidemiology and Prevention. Cancer Res 1992;52(24):6735-6740 PubMed/NCBI
  6. Ford AC, Yuan Y, Moayyedi P. Long-Term Impact of Helicobacter pylori Eradication Therapy on Gastric Cancer Incidence and Mortality in Healthy Infected Individuals: A Meta-Analysis Beyond 10 Years of Follow-Up. Gastroenterology 2022;163(3):754-756.e1 View Article PubMed/NCBI
  7. Yang L, Kartsonaki C, Yao P, de Martel C, Plummer M, Chapman D, et al. The relative and attributable risks of cardia and non-cardia gastric cancer associated with Helicobacter pylori infection in China: a case-cohort study. Lancet Public Health 2021;6(12):e888-e896 View Article PubMed/NCBI
  8. Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: An updated guideline for reporting systematic reviews. Int J Surg 2021;88:105906 View Article PubMed/NCBI
  9. Higgins JPT, Morgan RL, Rooney AA, Taylor KW, Thayer KA, Silva RA, et al. A tool to assess risk of bias in non-randomized follow-up studies of exposure effects (ROBINS-E). Environ Int 2024;186:108602 View Article PubMed/NCBI
  10. Chen MJ, Wu DC, Lin JM, Wu MT, Sung FC. Etiologic factors of gastric cardiac adenocarcinoma among men in Taiwan. World J Gastroenterol 2009;15(43):5472-5480 View Article PubMed/NCBI
  11. Cho SJ, Choi IJ, Kim CG, Lee JY, Kook MC, Seong MW, et al. Helicobacter pylori Seropositivity Is Associated with Gastric Cancer Regardless of Tumor Subtype in Korea. Gut Liver 2010;4(4):466-474 View Article PubMed/NCBI
  12. Derakhshan MH, Malekzadeh R, Watabe H, Yazdanbod A, Fyfe V, Kazemi A, et al. Combination of gastric atrophy, reflux symptoms and histological subtype indicates two distinct aetiologies of gastric cardia cancer. Gut 2008;57(3):298-305 View Article PubMed/NCBI
  13. Gao P, Cai N, Yang X, Yuan Z, Zhang T, Lu M, et al. Association of Helicobacter pylori and gastric atrophy with adenocarcinoma of the esophagogastric junction in Taixing, China. Int J Cancer 2022;150(2):243-252 View Article PubMed/NCBI
  14. Horii T, Koike T, Abe Y, Kikuchi R, Unakami H, Iijima K, et al. Two distinct types of cancer of different origin may be mixed in gastroesophageal junction adenocarcinomas in Japan: evidence from direct evaluation of gastric acid secretion. Scand J Gastroenterol 2011;46(6):710-719 View Article PubMed/NCBI
  15. Inoue M, Sawada N, Goto A, Shimazu T, Yamaji T, Iwasaki M, et al. High-Negative Anti-Helicobacter pylori IgG Antibody Titers and Long-Term Risk of Gastric Cancer: Results from a Large-Scale Population-Based Cohort Study in Japan. Cancer Epidemiol Biomarkers Prev 2020;29(2):420-426 View Article PubMed/NCBI
  16. Kamangar F, Qiao YL, Blaser MJ, Sun XD, Katki H, Fan JH, et al. Helicobacter pylori and oesophageal and gastric cancers in a prospective study in China. Br J Cancer 2007;96(1):172-176 View Article PubMed/NCBI
  17. Kato M, Asaka M, Shimizu Y, Nobuta A, Takeda H, Sugiyama T, et al. Relationship between Helicobacter pylori infection and the prevalence, site and histological type of gastric cancer. Aliment Pharmacol Ther 2004;20(Suppl 1):85-89 View Article PubMed/NCBI
  18. Kikuchi S, Wada O, Nakajima T, Nishi T, Kobayashi O, Konishi T, et al. Serum anti-Helicobacter pylori antibody and gastric carcinoma among young adults. Research Group on Prevention of Gastric Carcinoma among Young Adults. Cancer 1995;75(12):2789-2793 View Article PubMed/NCBI
  19. Kikuchi S, Nakajima T, Kobayashi O, Yamazaki T, Kikuichi M, Mori K, et al. Effect of age on the relationship between gastric cancer and Helicobacter pylori. Tokyo Research Group of Prevention for Gastric Cancer. Jpn J Cancer Res 2000;91(8):774-779 View Article PubMed/NCBI
  20. Kim HY, Cho BD, Chang WK, Kim DJ, Kim YB, Park CK, et al. Helicobacter pylori infection and the risk of gastric cancer among the Korean population. J Gastroenterol Hepatol 1997;12(2):100-103 View Article PubMed/NCBI
  21. Kim JY, Lee HS, Kim N, Shin CM, Lee SH, Park YS, et al. Prevalence and clinicopathologic characteristics of gastric cardia cancer in South Korea. Helicobacter 2012;17(5):358-368 View Article PubMed/NCBI
  22. Komoto K, Haruma K, Kamada T, Tanaka S, Yoshihara M, Sumii K, et al. Helicobacter pylori infection and gastric neoplasia: correlations with histological gastritis and tumor histology. Am J Gastroenterol 1998;93(8):1271-1276 View Article PubMed/NCBI
  23. Lee BM, Jang JJ, Kim JS, You YC, Chun SA, Kim HS, et al. Association of Helicobacter pylori infection with gastric adenocarcinoma. Jpn J Cancer Res 1998;89(6):597-603 View Article PubMed/NCBI
  24. Shakeri R, Malekzadeh R, Nasrollahzadeh D, Pawlita M, Murphy G, Islami F, et al. Multiplex H. pylori Serology and Risk of Gastric Cardia and Noncardia Adenocarcinomas. Cancer Res 2015;75(22):4876-4883 View Article PubMed/NCBI
  25. Shibata T, Imoto I, Ohuchi Y, Taguchi Y, Takaji S, Ikemura N, et al. Helicobacter pylori infection in patients with gastric carcinoma in biopsy and surgical resection specimens. Cancer 1996;77(6):1044-1049 PubMed/NCBI
  26. Shin A, Shin HR, Kang D, Park SK, Kim CS, Yoo KY. A nested case-control study of the association of Helicobacter pylori infection with gastric adenocarcinoma in Korea. Br J Cancer 2005;92(7):1273-1275 View Article PubMed/NCBI
  27. Suzuki G, Cullings H, Fujiwara S, Hattori N, Matsuura S, Hakoda M, et al. 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. Cancer Epidemiol Biomarkers Prev 2007;16(6):1224-1228 View Article PubMed/NCBI
  28. Wu IC, Wu DC, Yu FJ, Wang JY, Kuo CH, Yang SF, et al. Association between Helicobacter pylori seropositivity and digestive tract cancers. World J Gastroenterol 2009;15(43):5465-5471 View Article PubMed/NCBI
  29. Xie S, Wang S, Xue L, Middleton DRS, Guan C, Hao C, et al. Helicobacter pylori Is Associated With Precancerous and Cancerous Lesions of the Gastric Cardia Mucosa: Results of a Large Population-Based Study in China. Front Oncol 2020;10:205 View Article PubMed/NCBI
  30. Yamaoka Y, Kodama T, Kashima K, Graham DY. Antibody against Helicobacter pylori CagA and VacA and the risk for gastric cancer. J Clin Pathol 1999;52(3):215-218 View Article PubMed/NCBI
  31. Yuan JM, Yu MC, Xu WW, Cockburn M, Gao YT, Ross RK. 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. Cancer Epidemiol Biomarkers Prev 1999;8(7):621-624 PubMed/NCBI
  32. Yan X, Zeng H, Li H, Cao M, Yang F, He S, et al. The current infection with Helicobacter pylori and association with upper gastrointestinal lesions and risk of upper gastrointestinal cancer: Insights from multicenter population-based cohort study. Int J Cancer 2024;155(7):1203-1211 View Article PubMed/NCBI
  33. Haruma K, Komoto K, Kamada T, Ito M, Kitadai Y, Yoshihara M, et al. Helicobacter pylori infection is a major risk factor for gastric carcinoma in young patients. Scand J Gastroenterol 2000;35(3):255-259 View Article PubMed/NCBI
  34. Limburg P, Qiao Y, Mark S, Wang G, Perez-Perez G, Blaser M, et al. Helicobacter pylori seropositivity and subsite-specific gastric cancer risks in Linxian, China. J Natl Cancer Inst 2001;93(3):226-233 View Article PubMed/NCBI
  35. Sasazuki S, Inoue M, Iwasaki M, Otani T, Yamamoto S, Ikeda S, et al. Effect of Helicobacter pylori infection combined with CagA and pepsinogen status on gastric cancer development among Japanese men and women: a nested case-control study. Cancer Epidemiol Biomarkers Prev 2006;15(7):1341-1347 View Article PubMed/NCBI
  36. Ren JS, Kamangar F, Qiao YL, Taylor PR, Liang H, Dawsey SM, et al. Serum pepsinogens and risk of gastric and oesophageal cancers in the General Population Nutrition Intervention Trial cohort. Gut 2009;58(5):636-642 View Article PubMed/NCBI
  37. Yao P, Kartsonaki C, Butt J, Jeske R, de Martel C, Plummer M, et al. Helicobacter pylori multiplex serology and risk of non-cardia and cardia gastric cancer: a case-cohort study and meta-analysis. Int J Epidemiol 2023;52(4):1197-1208 View Article PubMed/NCBI
  38. Kartsonaki C, Yao P, Butt J, Jeske R, de Martel C, Plummer M, et al. Infectious pathogens and risk of esophageal, gastric and duodenal cancers and ulcers in China: A case-cohort study. Int J Cancer 2024;154(8):1423-1432 View Article PubMed/NCBI
  39. Peleteiro B, Lunet N, Barros R, La Vecchia C, Barros H. Factors contributing to the underestimation of Helicobacter pylori-associated gastric cancer risk in a high-prevalence population. Cancer Causes Control 2010;21(8):1257-1264 View Article PubMed/NCBI
  40. Morais S, Costa A, Albuquerque G, Araújo N, Tsugane S, Hidaka A, et al. “True” Helicobacter pylori infection and non-cardia gastric cancer: A pooled analysis within the Stomach Cancer Pooling (StoP) Project. Helicobacter 2022;27(3):e12883 View Article PubMed/NCBI
  41. Kusano C, Gotoda T, Khor CJ, Katai H, Kato H, Taniguchi H, et al. Changing trends in the proportion of adenocarcinoma of the esophagogastric junction in a large tertiary referral center in Japan. J Gastroenterol Hepatol 2008;23(11):1662-1665 View Article PubMed/NCBI
  42. Peng X, Chen W, Chen Z, Liang Z, Wei K. Epidemiology of gastric cardia cancer in China. Chinese Archives of General Surgery (Electronic Edition) 2014;2014(2):156-159 View Article
  43. Helicobacter and Cancer Collaborative Group. Gastric cancer and Helicobacter pylori: a combined analysis of 12 case control studies nested within prospective cohorts. Gut 2001;49(3):347-353 View Article PubMed/NCBI
  44. Cavaleiro-Pinto M, Peleteiro B, Lunet N, Barros H. Helicobacter pylori infection and gastric cardia cancer: systematic review and meta-analysis. Cancer Causes Control 2011;22(3):375-387 View Article PubMed/NCBI
  45. Bae JM, Kim EH. Helicobacter pylori Infection and Risk of Gastric Cancer in Korea: A Quantitative Systematic Review. J Prev Med Public Health 2016;49(4):197-204 View Article PubMed/NCBI
  46. Ma S, Ma Q, Li J, Wei W. [Meta-analysis on relationship between Helicobacter pylori infection and esophagogastric junction adenocarcinoma]. Zhonghua Liu Xing Bing Xue Za Zhi 2016;37(3):418-424 View Article PubMed/NCBI
  47. Gu J, He F, Clifford GM, Li M, Fan Z, Li X, et al. A systematic review and meta-analysis on the relative and attributable risk of Helicobacter pylori infection and cardia and non-cardia gastric cancer. Expert Rev Mol Diagn 2023;23(12):1251-1261 View Article PubMed/NCBI
  48. Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin 2021;71(3):209-249 View Article PubMed/NCBI
  49. Siewert JR, Stein HJ. Classification of adenocarcinoma of the oesophagogastric junction. Br J Surg 1998;85(11):1457-1459 View Article PubMed/NCBI
  50. Sugano K, Spechler SJ, El-Omar EM, McColl KEL, Takubo K, Gotoda T, et al. Kyoto international consensus report on anatomy, pathophysiology and clinical significance of the gastro-oesophageal junction. Gut 2022;71(8):1488-1514 View Article PubMed/NCBI
  51. Hansen S, Vollset SE, Derakhshan MH, Fyfe V, Melby KK, Aase S, et al. Two distinct aetiologies of cardia cancer; evidence from premorbid serological markers of gastric atrophy and Helicobacter pylori status. Gut 2007;56(7):918-925 View Article PubMed/NCBI
  52. Demicco EG, Farris AB, Baba Y, Agbor-Etang B, Bergethon K, Mandal R, et al. The dichotomy in carcinogenesis of the distal esophagus and esophagogastric junction: intestinal-type vs cardiac-type mucosa-associated adenocarcinoma. Mod Pathol 2011;24(9):1177-1190 View Article PubMed/NCBI
  53. Urabe M, Ushiku T, Shinozaki-Ushiku A, Iwasaki A, Yamazawa S, Yamashita H, et al. Adenocarcinoma of the esophagogastric junction and its background mucosal pathology: A comparative analysis according to Siewert classification in a Japanese cohort. Cancer Med 2018;7(10):5145-5154 View Article PubMed/NCBI
  54. Gu J, Xie S, Wang S, Xue L, Zhou J, Li M, et al. Surveillance of premalignant gastric cardia lesions: A population-based prospective cohort study in China. Int J Cancer 2021;149(9):1639-1648 View Article PubMed/NCBI
  55. Zhao J, Zhao J, Du F, Zhang Y, Shen G, Zhu H, et al. Cardia and Non-Cardia Gastric Cancer Have Similar Stage-for-Stage Prognoses After R0 Resection: a Large-Scale, Multicenter Study in China. J Gastrointest Surg 2016;20(4):700-707 View Article PubMed/NCBI
  56. González CA, Megraud F, Buissonniere A, Lujan Barroso L, Agudo A, Duell EJ, et al. Helicobacter pylori infection assessed by ELISA and by immunoblot and noncardia gastric cancer risk in a prospective study: the Eurgast-EPIC project. Ann Oncol 2012;23(5):1320-1324 View Article PubMed/NCBI
  57. Huang Q, Read M, Gold JS, Zou XP. Unraveling the identity of gastric cardiac cancer. J Dig Dis 2020;21(12):674-686 View Article PubMed/NCBI
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  • Cancer Screening and Prevention
  • pISSN 2993-6314
  • eISSN 2835-3315

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Helicobacter pylori Infection and Risk of Cardia Gastric Cancer in Asian Countries: A Systematic Review and Meta-analysis

Yinnan Zhu, Yuan Ding, Qiliu Qian, Wanyue Zhang, Qingxia Wang, Ruihua Shi
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