Skip to main content
  • AACR Publications
    • Blood Cancer Discovery
    • Cancer Discovery
    • Cancer Epidemiology, Biomarkers & Prevention
    • Cancer Immunology Research
    • Cancer Prevention Research
    • Cancer Research
    • Clinical Cancer Research
    • Molecular Cancer Research
    • Molecular Cancer Therapeutics

AACR logo

  • Register
  • Log in
  • Log out
  • My Cart
Advertisement

Main menu

  • Home
  • About
    • The Journal
    • AACR Journals
    • Subscriptions
    • Permissions and Reprints
  • Articles
    • OnlineFirst
    • Current Issue
    • Past Issues
    • Meeting Abstracts
    • Collections
      • COVID-19 & Cancer Resource Center
      • Must- Read Articles
      • "Best of" Collection
      • Editors' Picks
  • For Authors
    • Information for Authors
    • Author Services
    • Best of: Author Profiles
    • Submit
  • Alerts
    • Table of Contents
    • Editors' Picks
    • OnlineFirst
    • Citation
    • Author/Keyword
    • RSS Feeds
    • My Alert Summary & Preferences
  • News
    • Cancer Discovery News
  • COVID-19
  • Webinars
  • Search More

    Advanced Search

  • AACR Publications
    • Blood Cancer Discovery
    • Cancer Discovery
    • Cancer Epidemiology, Biomarkers & Prevention
    • Cancer Immunology Research
    • Cancer Prevention Research
    • Cancer Research
    • Clinical Cancer Research
    • Molecular Cancer Research
    • Molecular Cancer Therapeutics

User menu

  • Register
  • Log in
  • Log out
  • My Cart

Search

  • Advanced search
Cancer Prevention Research
Cancer Prevention Research
  • Home
  • About
    • The Journal
    • AACR Journals
    • Subscriptions
    • Permissions and Reprints
  • Articles
    • OnlineFirst
    • Current Issue
    • Past Issues
    • Meeting Abstracts
    • Collections
      • COVID-19 & Cancer Resource Center
      • Must- Read Articles
      • "Best of" Collection
      • Editors' Picks
  • For Authors
    • Information for Authors
    • Author Services
    • Best of: Author Profiles
    • Submit
  • Alerts
    • Table of Contents
    • Editors' Picks
    • OnlineFirst
    • Citation
    • Author/Keyword
    • RSS Feeds
    • My Alert Summary & Preferences
  • News
    • Cancer Discovery News
  • COVID-19
  • Webinars
  • Search More

    Advanced Search

Research Article

Helicobacter pylori and Esophageal Cancer Risk: A Meta-analysis

Farhad Islami and Farin Kamangar
Farhad Islami
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Farin Kamangar
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
DOI: 10.1158/1940-6207.CAPR-08-0109 Published October 2008
  • Article
  • Figures & Data
  • Info & Metrics
  • PDF
Loading

Abstract

We conducted this meta-analysis to examine the association between Helicobacter pylori and esophageal adenocarcinoma (EAC) and esophageal squamous cell carcinoma. We searched the PubMed database, the ISI database, and the references of the selected articles. Case-control or nested case-control studies were selected if they used serology or endoscopic methods to detect H. pylori in the stomach and if control subjects were not restricted to upper gastrointestinal tract cancer or peptic ulcer disease patients. A total of 19 studies were used for this analysis. Summary odds ratios (OR) and 95% confidence intervals (95% CI) were calculated using the DerSimonian-Laird method. Q statistics and I2 statistics were calculated to examine heterogeneity. Subgroup analyses were conducted by CagA status. For EAC, the summary OR (95% CI) was 0.56 (0.46-0.68). There was little heterogeneity among studies (I2 = 15%). Further analysis showed that colonization with CagA-positive strains was inversely associated with EAC risk (OR, 0.41; 95% CI, 0.28-0.62) but colonization with CagA-negative strains was not (OR, 1.08; 95% CI, 0.76-1.53). For esophageal squamous cell carcinoma, the summary OR (95% CI) was 1.10 (0.78-1.55). However, there was substantial heterogeneity among studies (I2 = 73%), with statistically significant associations in both directions. Our results suggest an inverse association between CagA-positive H. pylori colonization and risk of EAC. The prominent decline of H. pylori colonization in the past few decades may be partly responsible for the recent increase in EAC incidence in Western countries.

Keywords
  • Helicobacter pylori
  • CagA
  • esophageal cancer
  • adenocarcinoma
  • squamous cell carcinoma
  • colonization

Since its discovery in the early 1980s (1), Helicobacter pylori has been associated with several benign and malignant gastrointestinal tract diseases. H. pylori is now a known cause of gastric and duodenal ulcers, noncardia gastric adenocarcinoma, and gastric MALT lymphoma (2). In addition, epidemiologic studies have investigated the association between H. pylori and other gastrointestinal malignancies, including pancreatic cancer (3, 4), colorectal cancer (5, 6), and esophageal cancer. Of these, the association with esophageal cancer has been examined in a larger number of studies and relatively consistent patterns of association are emerging. Systematic reviews will help in establishing such patterns.

With over 450,000 new cases annually, esophageal cancer is the 8th most common incident cancer in the world (7). The two main histologic types of esophageal cancer, esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC), have distinct geographic and demographic patterns. ESCC constitutes the large majority of all esophageal cancer cases in the world (7, 8) and more than 90% of the cases in some high-risk areas of the world, such as China (9) and Iran (10). EAC constitutes the minority of esophageal cancer cases in the world, but approximately half of the cases in some Western countries, such as the United States and the United Kingdom, are of this type (11–13). There is also a large body of evidence suggesting that the risk factors for these two cancer types may be different. For example, alcohol consumption is a strong risk factor for ESCC but its association with EAC is unclear (14, 15). Therefore, the associations of any potential causal factors should be evaluated separately for these two cancer types.

H. pylori resides in the stomach and can be detected with a number of invasive methods, such as histologic examination or urease test on gastric antral biopsies, or by noninvasive methods, such as serologic tests (16). Of these, positive serologic tests indicate past or current colonization, whereas other methods indicate only current colonization of H. pylori in the stomach. Because of the low cost, the ability to detect previous exposure, and the availability of serum in epidemiologic studies, serologic tests are especially useful in such studies.

There are different strains of H. pylori. The genome of CagA-positive strains contains the cag pathogenicity island. This island includes approximately 31 putative genes, including cagA—the gene that encodes the CagA protein (17). CagA-positive strains confer a higher risk of noncardia gastric cancer than CagA-negative strains (18). Likewise, the association between CagA-positive and CagA-negative strains with other cancers may be different (19) and should be considered in analyses.

We conducted this meta-analysis to summarize the published literature on the association between H. pylori, detected by different methods, and esophageal cancer. We analyzed and report the results separately for ESCC and EAC. We also report the associations by CagA status.

Materials and Methods

Selection of studies

We conducted a comprehensive search by examining the PubMed and ISI-Web of Knowledge databases for all case-control or cohort studies that have been published on the association between H. pylori colonization in the stomach and risk of esophageal cancer. All results were updated on February 12, 2008. The following terms were used in the PubMed Database search: [“Helicobacter pylori” [MeSH] OR (Campylobacter pylori) OR (H Pylori) OR (H. Pylori)] AND [“Esophageal Neoplasms” [MeSH] OR (Cancer of Esophagus) OR (Cancer of the Esophagus) OR (Esophageal Cancer) OR (Esophagus Cancer) OR (Esophagus Neoplasm) OR (Neoplasms, Esophageal)]. The same terms were used to search text words in the ISI Database. The search was repeated by replacing Esophagus with Oesophagus, and Esophageal with Oesophageal. In addition, references cited in the identified articles were searched manually. Both authors reviewed the search results to reduce the possibility of missing the published articles. Where data were missing, we contacted the authors for the relevant information. Using these approaches, reports on H. pylori in relation to esophageal cancer were found in 35 full-text articles (19–53).

Inclusion criteria were (a) testing for the presence of H. pylori in the stomach using invasive or noninvasive methods and (b) including control subjects without upper gastrointestinal cancers or peptic ulcer disease. Based on these criteria, three studies were excluded because they examined the presence of H. pylori only in esophageal tissue samples (but not in the stomach; refs. 30, 43, 49). Six studies were excluded because they had no control subjects or because all control subjects had upper gastrointestinal tract cancers or peptic ulcers (22, 26, 34, 37–39). Six more studies (19, 24, 32, 40, 44, 51) were excluded because the H. pylori assay results were also reported in other publications (23, 27, 36, 41, 50, 53). Finally, one study was excluded because cancers of the proximal 5 cm of stomach were considered as esophageal cancer (29). Therefore, a total of 19 studies were used for calculating summary statistics.

Data extraction and statistical analysis

We compared H. pylori positivity in esophageal cancer cases and controls. H. pylori positivity was defined as having evidence for H. pylori colonization by direct (invasive) examination of the gastric antral tissue or being seropositive for IgG antibodies against whole-cell antigen. In an additional analysis, we used a broader definition of H. pylori positivity, defined as having evidence for H. pylori colonization by direct examination of the gastric antral tissue, being seropositive for IgG antibodies against H. pylori whole-cell antigen, or being seropositive for IgG antibodies against CagA. We chose this broader definition because individuals who are seronegative for antibodies against whole-cell antigen but are seropositive for antibodies against CagA may in fact be positive for H. pylori (54). Where data were available, we compared the presence of CagA-positive strains (versus no H. pylori), and the presence of CagA-negative strains (versus no H. pylori) between case and control subjects. In all studies, CagA positivity was determined using IgG antibodies.

We calculated odds ratios (OR) and 95% confidence intervals (95% CI) for the association between each of the exposures noted above and esophageal cancer. ORs and 95% CIs were calculated for each individual study and for all studies combined. We used both random-effects models (DerSimonian-Laird method) and fixed-effects models (Mantel-Haenszel method) to calculate summary ORs and 95% CIs. Because these two methods provided qualitatively similar results, we chose random-effects models, which are more conservative than fixed-effects models (55), to present forest plots and subgroup analyses described in the text.

We conducted several subgroup analyses. In a number of studies, the control subjects were selected from among clinic patients who were endoscoped because of upper gastrointestinal tract symptoms. Use of such control subjects may bias results because the H. pylori colonization rate in such control subjects may be different from the rate in the general population. Therefore, subgroup analyses were done that included only population-based studies. We also did subgroup analyses for studies from Western (European and American) and Eastern (Asian) countries, which may have different H. pylori positivity rates in their general populations. High prevalence of H. pylori colonization among controls may conceal an association between H. pylori and disease, especially if the association is not very strong. Only serologic studies are able to detect past exposure to H. pylori. Therefore, we also calculated summary ORs (95% CIs) for the subgroup of studies that had used serologic tests. H. pylori colonization rate is usually higher in older subjects, mostly because of cohort effects. Therefore, subgroup analyses were done for studies that had used age-matched controls (group-matched or individual-matched). Differentiating between EAC and gastric cardia adenocarcinoma can be challenging. To differentiate between the two, some studies required the presence of Barrett's esophagus for diagnosis of EAC. We conducted a subgroup analysis using these studies. Because the association between H. pylori and esophageal cancer could potentially be confounded by other factors, e.g., socioeconomic status, we also calculated and present the summary of adjusted ORs (95% CIs) for studies that provided adjusted results.

We plotted Begg's funnel plot to examine small study effects (56). We also used Begg and Mazumdar's method (57) to calculate P for rank correlation and Egger's weighted regression method (58) to calculate P for bias. For sensitivity analysis, we excluded smaller studies and recalculated the summary ORs (95% CIs) using only larger studies.

To examine heterogeneity among studies, the Q statistic (using Mantel-Haenszel weights) and the I2 statistic (59) were calculated. All analyses were done using STATA software, version 10.0 (StataCorp LP). Throughout the article, two-sided P values <0.05 were considered as statistically significant.

Results

Summary characteristics of the 19 studies that were included in this analysis are presented in Table 1. Most studies used serologic tests to determine prior or current stomach colonization with H. pylori and to determine CagA status. Approximately half of the studies were population based, whereas the other half were clinic based.

View this table:
  • View inline
  • View popup
Table 1

Study characteristics

Esophageal adenocarcinoma

Figure 1A and Table 2 show the results for the association between H. pylori and EAC. A total of 13 studies with 840 cases and 2,890 controls were included in this analysis. The OR point estimate for each individual study was below 1 (Fig. 1A), and the overall random effects and fixed effects ORs (95% CIs) were 0.56 (0.46-0.68) and 0.55 (0.47-0.66), respectively. For the overall association, the I2 statistic was 15%, suggesting little heterogeneity, and the P value associated with the Q statistic was 0.29, showing no statistically significant heterogeneity (Table 2).

Fig. 1
  • Download figure
  • Open in new tab
  • Download powerpoint
Fig. 1

Forest plot and Begg's funnel for the association between H. pylori and esophageal cancer. Studies are sorted in order of publication year. A, esophageal adenocarcinoma. B, esophageal squamous cell carcinoma.

View this table:
  • View inline
  • View popup
Table 2

Summary statistics for the association between H. pylori and esophageal adenocarcinoma

Begg's funnel plot for the association between H. pylori and EAC is also shown in Fig. 1A. This figure shows the logarithm of the odds ratio (Y axis) versus its SE (X axis). Smaller studies have larger SEs; therefore, points representing these studies are in the right-hand side of the graph. The distribution of the dots on this graph was reasonably symmetric, suggesting no strong evidence for publication bias. Also, there was no evidence for bias using either Begg and Mazumdar's method (P for rank correlation = 0.76) or Egger's weighted regression method (P for bias = 0.71). After excluding small studies, defined as those having a SE >0.5, the summary OR (95% CI) for H. pylori positivity was 0.58 (0.47-0.73).

Table 2 also shows the results of subgroup analyses. Similar to the overall association, every subgroup analysis showed an inverse association between H. pylori positivity and EAC risk. For population-based studies, the OR (95% CI) was 0.58 (0.43-0.76). The ORs (95% CIs) for Western and Eastern studies were 0.57 (0.47-0.70) and 0.32 (0.10-1.02), respectively. Only one study (25) was from an Eastern country. The summary OR (95% CI) for studies that used serologic tests was 0.59 (0.48-0.73). Among the studies that matched for age, the summary OR (95% CI) was 0.58 (0.46-0.75). The summary OR (95% CI) for studies that included Barrett's esophagus in their diagnostic criteria (20, 36, 45, 48, 53) was 0.44 (0.33-0.58). Analysis of adjusted ORs (95% CIs) yielded a summary OR (95% CI) of 0.50 (0.34-0.74). There was no evidence for significant heterogeneity in the subgroup analyses, except for the adjusted analyses, which showed a marginally significant Q statistic (P = 0.04).

When we used the broader definition of H. pylori positivity (being positive for H. pylori or CagA), there was little change in the results, and the overall random-effects OR (95% CI) was 0.56 (0.45-0.69). There was also an inverse association between H. pylori and EAC in all subgroup analyses (results not shown).

Eight of the studies reported on antibodies to CagA, and in five of these, the simultaneous status of IgG antibodies to both CagA and whole-cell antigen was known. In this latter group of studies, the summary ORs (95% CIs) for carrying CagA-negative and CagA-positive H. pylori strains, versus being H. pylori negative, were 1.08 (0.76-1.53) and 0.41 (0.28-0.62), respectively. These two summary ORs were statistically significantly different from each other (P < 0.01). Figure 2A shows the associations between CagA-negative and CagA-positive strains and EAC separately. All five studies show inverse associations for CagA-positive strains, but the results for CagA-negative strains are mixed.

Fig. 2
  • Download figure
  • Open in new tab
  • Download powerpoint
Fig. 2

The association between CagA-positive and CagA-negative strains and esophageal cancer. Studies are sorted in order of publication year. A, esophageal adenocarcinoma. B, esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma

Figure 1B and Table 3 show the results for the association between H. pylori and ESCC. Nine studies, with a total of 921 cases and 2,743 controls, were included in this analysis. As shown in Fig. 1B, the results varied substantially, on both sides of the neutral line, and the ORs (95% CIs) ranged from 0.37 (0.22-0.62) to 2.11 (1.15-3.90), statistically significant in opposite directions. The overall summary ORs (95% CIs) using the random-effects and fixed-effects models were 1.10 (0.78-1.55) and 1.07 (0.91-1.26), respectively. Indices of heterogeneity are shown in Table 3. For the overall analysis, the Q statistic was significant (P < 0.01) and the I2 statistic showed a high variation (73%) among study results.

View this table:
  • View inline
  • View popup
Table 3

Summary statistics for the association between H. pylori and esophageal squamous cell carcinoma

Begg's funnel plot for the association between H. pylori and ESCC is shown in Fig. 1B. The distribution of the dots around the summary line was symmetric, and there was no evidence of bias using either Begg's method (P = 0.47) or Egger's method (P for bias = 0.84). All studies had a SE of <0.5.

Subgroup analysis results are shown in Table 3. The summary OR (95% CI) for population-based studies was 1.00 (0.62-1.60). The ORs (95% CIs) for Western and Eastern studies were 1.17 (0.71-1.95) and 1.05 (0.63-1.77), respectively. The OR (95% CI) for studies that used serologic tests was 1.10 (0.78-1.55). The summary OR (95% CI) for studies that matched for age was 1.28 (0.89-1.83). When the adjusted ORs were analyzed, the overall OR (95% CI) was 0.99 (0.67-1.45). Similar to the overall analysis, the I2 and Q statistics suggested high and statistically significant heterogeneity in the subgroup analyses.

When the broader definition of H. pylori positivity was used, the random-effects OR for the overall association changed only slightly and remained nonsignificant. However, when studies were classified by geographic region, there was a statistically significant association between H. pylori and ESCC in Western studies, with an OR (95% CI) of 1.65 (1.17-2.32). Other subgroup analyses yielded results that were qualitatively similar to those found with the earlier definition of H. pylori positivity (results not shown).

Four studies reported on CagA results, and in all of them the simultaneous status of antibodies to CagA and whole-cell were known. Two of these studies dominated the results (Fig. 2B). The summary ORs (95% CIs) for carrying CagA-negative and CagA-positive strains, versus being H. pylori–negative, were 1.41 (1.00-1.97) and 1.01 (0.80-1.27), respectively. These two summary OR point estimates were not statistically significantly different from each other.

Discussion

The results of this meta-analysis suggest that colonization of the stomach with CagA-positive strains of H. pylori may protect against EAC.

H. pylori has coexisted with modern humans since their origin (60), and once it could be found in the stomachs of most humans. With advances in sanitation and use of antibiotics, however, this bacterium is rapidly disappearing from human populations (61), especially in Western countries. In the United States, for example, data from the third National Health and Nutritional Examination Survey (1988-1991) showed that serum samples from 57% of the population older than 70 years of age, versus 17% of the population between 20 and 29 years of age, were positive for IgG antibodies against H. pylori (62). More recent data from the National Health and Nutritional Examination Survey 1999-2000 show a positive IgG seroprevalence of only 5% in children younger than 10 years old who were born in the 1990s (63). Given that H. pylori colonization in most people occurs before the age of 10 years (64), these numbers show a substantial decline in H. pylori in a period of 70 years. This decrease mostly reflects a cohort effect (65) rather than eradication of H. pylori in individuals over time.

With changes in the prevalence of H. pylori, incidence rates of diseases caused, or prevented, by this organism change. H. pylori is a known cause of noncardia gastric cancer (66). Incidence rates of this cancer have been sharply declining in most parts of the world in the past few decades (7). In contrast, rates of EAC have steeply increased in Western countries during this same period (13, 67). Once a rare cancer, EAC now constitutes approximately half of all esophageal cancer cases in some Western populations (11–13). Our results suggest that CagA-positive strains of H. pylori, which constitute the majority of H. pylori strains, may protect against EAC, and that increasing EAC rates may be partly due to the decline of H. pylori in human populations. In parallel with EAC rates, the incidence rates of gastric cardia adenocarcinoma, another cancer inversely associated with H. pylori prevalence (68), are increasing in some Western countries (67). However, it is unclear whether this latter inverse association is real or it merely reflects misclassification of EAC for gastric cardia adenocarcinoma (33, 69). Another observation consistent with the hypothesis that H. pylori disappearance is contributing to the increased EAC rates is that EAC rates are still low in most developing countries (9, 10), where H. pylori is still common.

H. pylori may decrease risk of EAC by reducing acid production in the stomach and hence reducing acid reflux to the esophagus (19). It may also reduce EAC risk by decreasing the production of the hormone ghrelin, which is mostly secreted from the stomach and stimulates appetite (70). A reduction in the level of ghrelin may lead to lower rates of obesity, an important risk factor for EAC (71).

The protective association of H. pylori with EAC or gastric cardia adenocarcinoma may be part of a broader phenomenon. The long history of coexistence of this organism with humans, despite its disease-causing potential, may suggest that H. pylori also has some beneficial effects to humans (61), including possible roles in reducing diarrheal diseases and asthma (63, 72, 73). Therefore, in this article, we have used the term H. pylori “colonization,” rather than “infection,” to describe the presence of H. pylori living in the stomach. The reciprocal link of H. pylori with both EAC and asthma may be due to lower acid reflux, which is a risk factor for both diseases, or it could be due to modulation of the hormones leptin and ghrelin, which have immunoregulatory effects (reviewed in refs. 72, 74).

The decline of H. pylori colonization can only partly explain the sharp increase in EAC incidence rates. With an OR of 0.5, even if H. pylori entirely disappeared, EAC incidence could increase at most by 2-fold; thus, part of the nearly 4-fold increased incidence observed in some populations (67) must be due to other reasons. Recent epidemiologic studies have found three important risk factors for EAC, namely gastroesophageal reflux, obesity, and smoking (14, 15, 71, 75). Whether, and how much, a change in the prevalence of these factors has contributed to the surge of EAC cases in the past few decades is still debated.

We conducted several analyses to examine the robustness of the association between H. pylori and EAC. The point estimate of the OR for each individual study in the meta-analysis was lower than 1, and there was little heterogeneity among these studies. Subgroup analyses also showed remarkably consistent ORs. When data analysis was limited to population-based studies, to studies from Western or Eastern countries, to studies that used serologic tests to determine exposure, to studies that matched for age, to larger studies, or to studies that included Barrett's esophagus in their diagnostic criteria, the summary OR remained lower than 0.60. When we used adjusted estimates, the summary OR was 0.50. Therefore, the results were quite robust. Likewise, using the broader definition of H. pylori positivity had very little or no impact on the results. We did not find any evidence for publication bias by using funnel plots or formal statistical tests.

CagA-positive strains of H. pylori have been disappearing faster than the CagA-negative ones (76). Interestingly, the inverse association between H. pylori and EAC was seen only with CagA-positive strains. Forest plots showed that this pattern was consistent across studies. It should be noted, however, that only 5 of the 13 selected studies could be used for comparing the effects of CagA-positive and CagA-negative strains. Therefore, more studies may still be needed to confirm this pattern. As discussed earlier, CagA-positive strains confer higher risk of noncardia gastric cancer than CagA-negative strains (18). Therefore, CagA-positive strains may also have stronger associations with other diseases that are caused, or prevented, by H. pylori. CagA protein can be delivered into gastric epithelial cells, and it may increase the risk of gastric cancer by increasing the turnover of the gastric epithelium (17). CagA-positive strains are also more likely to have the s1 allele of vacA, which encodes a molecule that affects epithelial cells (77) and may increase gastric cancer risk (78), and are also more likely to express the babA product, which controls adherence of H. pylori organisms to Lewisb antigens on gastric epithelial cells (77). The biological reasons for the inverse association between CagA-positive H. pylori and EAC need to be further investigated.

We found no overall association between H. pylori and ESCC risk. However, the point estimates differed substantially and qualitatively among studies, resulting in large heterogeneity indices. Limiting studies to population-based studies, studies from Western or Eastern countries, studies that used serologic tests, studies that matched for age, or studies using adjusted results made little change in summary estimates and did not reduce heterogeneity. Therefore, the source of the observed heterogeneity is unclear. Gastric colonization with CagA-positive strains was not associated with ESCC risk. Compared with H. pylori–negative subjects, CagA-negative strains were associated with a marginally significant increased risk of ESCC. However, the bulk of the data for the latter analysis came from only two studies, and further studies are needed to make more definitive conclusions. An association was observed in studies from Western countries when we used the broader definition of H. pylori positivity. Again, there were only four studies in this analysis, and further data are needed to have more confidence in the results.

One other meta-analysis has previously examined the association between H. pylori and esophageal cancer (79). Our meta-analysis differs from this previous evaluation in several respects. One difference is the choice of published articles. The two meta-analyses share only six articles that examined the association between H. pylori and EAC, and only four articles that examined the association between H. pylori and ESCC. We excluded several of the publications used in the previous meta-analysis because they included duplicate data from the same study; we substituted newer papers from some studies; and we included several additional recent studies. We also conducted multiple subgroup analyses to examine the robustness of our data to the choice of study methods and other factors. We also examined the effects of CagA-positive and CagA-negative strains of H. pylori separately versus H. pylori–negative subjects, rather than comparing CagA-positive subjects versus all other subjects. Despite these differences, both meta-analyses found that H. pylori protects against EAC and is not significantly related to ESCC risk. Also, both meta-analyses found that the association of H. pylori with EAC was largely homogeneous across studies, but there was substantial and statistically significant heterogeneity in results with respect to ESCC.

The strengths of this meta-analysis include the evaluation of 19 published studies with a large number of cases and controls, presenting multiple subgroup analyses, and using several methods to examine study heterogeneity and publication bias. This meta-analysis also has limitations. Combining observational studies conducted in different populations with various qualities of design to obtain summary ORs and 95% CIs can sometimes be misleading (80) and summary statistics need to be interpreted with caution (81). However, as mentioned above, at least for EAC, there was little evidence of heterogeneity and the results were robust to multiple subgroup analyses.

In conclusion, we found an inverse association between CagA-positive strains of H. pylori and risk of esophageal adenocarcinoma. The prominent decline of H. pylori colonization, especially CagA-positive strains, may be responsible for part of the recent increase in esophageal adenocarcinoma rates in Western countries.

Disclosure of Potential Conflicts of Interest

No potential conflicts of interest were disclosed.

Acknowledgments

We thank Dr. Sanford M. Dawsey for reviewing the manuscript and giving us his invaluable comments.

Footnotes

  • Grant support: National Cancer Institute, NIH.

  • Received June 10, 2008.
  • Revision received July 11, 2008.
  • Accepted August 4, 2008.
  • ©2008 American Association for Cancer Research.

References

  1. ↵
    1. Marshall BJ,
    2. Warren JR
    . Unidentified curved bacilli in the stomach of patients with gastritis and peptic ulceration. Lancet 1984;1:1311–5.
    OpenUrlCrossRefPubMed
  2. ↵
    1. Suerbaum S,
    2. Michetti P
    . Helicobacter pylori infection. N Engl J Med 2002;347:1175–86.
    OpenUrlCrossRefPubMed
  3. ↵
    1. Raderer M,
    2. Wrba F,
    3. Kornek G,
    4. et al
    . Association between Helicobacter pylori infection and pancreatic cancer. Oncology 1998;55:16–9.
    OpenUrlCrossRefPubMed
  4. ↵
    1. Stolzenberg-Solomon RZ,
    2. Blaser MJ,
    3. Limburg PJ,
    4. et al
    . Helicobacter pylori seropositivity as a risk factor for pancreatic cancer. J Natl Cancer Inst 2001;93:937–41.
    OpenUrlAbstract/FREE Full Text
  5. ↵
    1. Limburg PJ,
    2. Stolzenberg-Solomon RZ,
    3. Colbert LH,
    4. et al
    . Helicobacter pylori seropositivity and colorectal cancer risk: a prospective study of male smokers. Cancer Epidemiol Biomarkers Prev 2002;11:1095–9.
    OpenUrlAbstract/FREE Full Text
  6. ↵
    1. Shmuely H,
    2. Passaro D,
    3. Figer A,
    4. et al
    . Relationship between Helicobacter pylori CagA status and colorectal cancer. Am J Gastroenterol 2001;96:3406–10.
    OpenUrlCrossRefPubMed
  7. ↵
    1. Kamangar F,
    2. Dores GM,
    3. Anderson WF
    . Patterns of cancer incidence, mortality, and prevalence across five continents: defining priorities to reduce cancer disparities in different geographic regions of the world. J Clin Oncol 2006;24:2137–50.
    OpenUrlAbstract/FREE Full Text
  8. ↵
    1. Corley DA,
    2. Buffler PA
    . Oesophageal and gastric cardia adenocarcinomas: analysis of regional variation using the Cancer Incidence in Five Continents database. Int J Epidemiol 2001;30:1415–25.
    OpenUrlAbstract/FREE Full Text
  9. ↵
    1. Tran GD,
    2. Sun XD,
    3. Abnet CC,
    4. et al
    . Prospective study of risk factors for esophageal and gastric cancers in the Linxian general population trial cohort in China. Int J Cancer 2005;113:456–63.
    OpenUrlCrossRefPubMed
  10. ↵
    1. Islami F,
    2. Kamangar F,
    3. Aghcheli K,
    4. et al
    . Epidemiologic features of upper gastrointestinal tract cancer in northeastern Iran. Br J Cancer 2004;90:1402–6.
    OpenUrlCrossRefPubMed
  11. ↵
    1. Brown LM,
    2. Devesa SS
    . Epidemiologic trends in esophageal and gastric cancer in the United States. Surg Oncol Clin N Am 2002;11:235–56.
    OpenUrlPubMed
    1. Freedman ND,
    2. Abnet CC,
    3. Leitzmann MF,
    4. et al
    . A prospective study of tobacco, alcohol, and the risk of esophageal and gastric cancer subtypes. Am J Epidemiol 2007;165:1424–33.
    OpenUrlAbstract/FREE Full Text
  12. ↵
    1. Powell J,
    2. McConkey CC,
    3. Gillison EW,
    4. Spychal RT
    . Continuing rising trend in oesophageal adenocarcinoma. Int J Cancer 2002;102:422–7.
    OpenUrlCrossRefPubMed
  13. ↵
    1. Gammon MD,
    2. Schoenberg JB,
    3. Ahsan H,
    4. et al
    . Tobacco, alcohol, and socioeconomic status and adenocarcinomas of the esophagus and gastric cardia. J Natl Cancer Inst 1997;89:1277–84.
    OpenUrlAbstract/FREE Full Text
  14. ↵
    1. Vaughan TL,
    2. Davis S,
    3. Kristal A,
    4. Thomas DB
    . Obesity, alcohol, and tobacco as risk factors for cancers of the esophagus and gastric cardia: adenocarcinoma versus squamous cell carcinoma. Cancer Epidemiol Biomarkers Prev 1995;4:85–92.
    OpenUrlAbstract
  15. ↵
    1. Bickston SJ,
    2. Peura DA
    Diagnostic tests for Helicobacter pylori infection. UpTodate (http://www.uptodate.com). Last accessed: March 10, 2008.
  16. ↵
    1. Hatakeyama M
    . Oncogenic mechanisms of the Helicobacter pylori CagA protein. Nat Rev Cancer 2004;4:688–94.
    OpenUrlCrossRefPubMed
  17. ↵
    1. Huang JQ,
    2. Zheng GF,
    3. Sumanac K,
    4. Irvine EJ,
    5. Hunt RH
    . Meta-analysis of the relationship between cagA seropositivity and gastric cancer. Gastroenterology 2003;125:1636–44.
    OpenUrlCrossRefPubMed
  18. ↵
    1. Chow WH,
    2. Blaser MJ,
    3. Blot WJ,
    4. et al
    . An inverse relation between cagA+ strains of Helicobacter pylori infection and risk of esophageal and gastric cardia adenocarcinoma. Cancer Res 1998;58:588–90.
    OpenUrlAbstract/FREE Full Text
  19. ↵
    1. Anandasabapathy S,
    2. Jhamb J,
    3. Davila M,
    4. Wei C,
    5. Morris J,
    6. Bresalier R
    . Clinical and endoscopic factors predict higher pathologic grades of Barrett dysplasia. Cancer 2007;109:668–74.
    OpenUrlCrossRefPubMed
  20. ↵
    1. Anderson LA,
    2. Murphy SJ,
    3. Johnston BT,
    4. et al
    . Relationship between Helicobacter pylori infection and gastric atrophy and the stages of the oesophageal inflammation, metaplasia, adenocarcinoma sequence: results from the FINBAR case-control study. Gut 2008;57:734–9.
    OpenUrlAbstract/FREE Full Text
  21. ↵
    1. Cameron AJ,
    2. Souto EO,
    3. Smyrk TC
    . Small adenocarcinomas of the esophagogastric junction: association with intestinal metaplasia and dysplasia. Am J Gastroenterol 2002;97:1375–80.
    OpenUrlCrossRefPubMed
  22. ↵
    1. de Martel C,
    2. Llosa AE,
    3. Farr SM,
    4. et al
    . Helicobacter pylori infection and the risk of development of esophageal adenocarcinoma. J Infect Dis 2005;191:761–7.
    OpenUrlAbstract/FREE Full Text
  23. ↵
    1. de Martel C,
    2. Haggerty TD,
    3. Corley DA,
    4. Vogelman JH,
    5. Orentreich N,
    6. Parsonnet J
    . Serum ghrelin levels and risk of subsequent adenocarcinoma of the esophagus. Am J Gastroenterol 2007;102:1166–72.
    OpenUrlCrossRefPubMed
  24. ↵
    1. Derakhshan MH,
    2. Malekzadeh R,
    3. Watabe H,
    4. et al
    . Combination of gastric atrophy, reflux symptoms and histological subtype indicates two distinct aetiologies of gastric cardia cancer. Gut 2007;57:298–305.
    OpenUrlCrossRefPubMed
  25. ↵
    1. Driessen A,
    2. Van Raemdonck D,
    3. De Leyn P,
    4. et al
    . Are carcinomas of the cardia oesophageal or gastric adenocarcinomas? Eur J Cancer 2003;39:2487–94.
    OpenUrlCrossRefPubMed
  26. ↵
    1. El Omar EM,
    2. Rabkin CS,
    3. Gammon MD,
    4. et al
    . Increased risk of noncardia gastric cancer associated with proinflammatory cytokine gene polymorphisms. Gastroenterology 2003;124:1193–201.
    OpenUrlCrossRefPubMed
  27. ↵
    1. Fruh M,
    2. Zhou W,
    3. Zhai R,
    4. et al
    . Polymorphisms of inflammatory and metalloproteinase genes, Helicobacter pylori infection and the risk of oesophageal adenocarcinoma. Br J Cancer 2008;98:689–92.
    OpenUrlCrossRefPubMed
  28. ↵
    1. Grimley CE,
    2. Holder RL,
    3. Loft DE,
    4. Morris A,
    5. Nwokolo CU
    . Helicobacter pylori-associated antibodies in patients with duodenal ulcer, gastric and oesophageal adenocarcinoma. Eur J Gastroenterol Hepatol 1999;11:503–9.
    OpenUrlPubMed
  29. ↵
    1. Henihan RD,
    2. Stuart RC,
    3. Nolan N,
    4. Gorey TF,
    5. Hennessy TP,
    6. O'Morain CA
    . Barrett's esophagus and the presence of Helicobacter pylori. Am J Gastroenterol 1998;93:542–6.
    OpenUrlCrossRefPubMed
  30. ↵
    1. Iijima K,
    2. Koike T,
    3. Abe Y,
    4. et al
    . Extensive gastric atrophy: an increased risk factor for superficial esophageal squamous cell carcinoma in Japan. Am J Gastroenterol 2007;102:1603–9.
    OpenUrlCrossRefPubMed
  31. ↵
    1. Jansson C,
    2. Johansson AL,
    3. Nyren O,
    4. Lagergren J
    . Socioeconomic factors and risk of esophageal adenocarcinoma: a nationwide Swedish case-control study. Cancer Epidemiol Biomarkers Prev 2005;14:1754–61.
    OpenUrlAbstract/FREE Full Text
  32. ↵
    1. Kamangar F,
    2. Qiao YL,
    3. Blaser MJ,
    4. et al
    . Helicobacter pylori and oesophageal and gastric cancers in a prospective study in China. Br J Cancer 2007;96:172–6.
    OpenUrlCrossRefPubMed
  33. ↵
    1. Lord RV,
    2. Frommer DJ,
    3. Inder S,
    4. Tran D,
    5. Ward RL
    . Prevalence of Helicobacter pylori infection in 160 patients with Barrett's oesophagus or Barrett's adenocarcinoma. Aust N Z J Surg 2000;70:26–33.
    OpenUrlCrossRefPubMed
  34. ↵
    1. Oberg S,
    2. Peters JH,
    3. Nigro JJ,
    4. et al
    . Helicobacter pylori is not associated with the manifestations of gastroesophageal reflux disease. Arch Surg 1999;134:722–6.
    OpenUrlCrossRefPubMed
  35. ↵
    1. Peek RM Jr..,
    2. Vaezi MF,
    3. Falk GW,
    4. et al
    . Role of Helicobacter pylori cagA(+) strains and specific host immune responses on the development of premalignant and malignant lesions in the gastric cardia. Int J Cancer 1999;82:520–4.
    OpenUrlCrossRefPubMed
  36. ↵
    1. Quddus MR,
    2. Henley JD,
    3. Sulaiman RA,
    4. Palumbo TC,
    5. Gnepp DR
    . Helicobacter pylori infection and adenocarcinoma arising in Barrett's esophagus. Hum Pathol 1997;28:1007–9.
    OpenUrlCrossRefPubMed
    1. Robeycafferty SS,
    2. Ro JY,
    3. Cleary KR
    . The prevalence of Campylobacter pylori in gastric biopsies from cancer-patients. Mod Pathol 1989;2:473–6.
    OpenUrlPubMed
  37. ↵
    1. Ruol A,
    2. Parenti A,
    3. Zaninotto G,
    4. et al
    . Intestinal metaplasia is the probable common precursor of adenocarcinoma in Barrett esophagus and adenocarcinoma of the gastric cardia. Cancer 2000;88:2520–8.
    OpenUrlCrossRefPubMed
  38. ↵
    1. Siman JH,
    2. Forsgren A,
    3. Berglund G,
    4. Floren CH
    . Helicobacter pylori infection is associated with a decreased risk of developing oesophageal neoplasms. Helicobacter 2001;6:310–6.
    OpenUrlCrossRefPubMed
  39. ↵
    1. Siman JH,
    2. Engstrand L,
    3. Berglund G,
    4. Forsgren A,
    5. Floren CH
    . Helicobacter pylori and CagA seropositivity and its association with gastric and oesophageal carcinoma. Scand J Gastroenterol 2007;42:933–40.
    OpenUrlCrossRefPubMed
  40. ↵
    1. Talley NJ,
    2. Zinsmeister AR,
    3. Weaver A,
    4. et al
    . Gastric adenocarcinoma and Helicobacter pylori infection. J Natl Cancer Inst 1991;83:1734–9.
    OpenUrlAbstract/FREE Full Text
  41. ↵
    1. Torrado J,
    2. Ruiz B,
    3. Garay J,
    4. et al
    . Blood-group phenotypes, sulfomucins, and Helicobacter pylori in Barrett's esophagus. Am J Surg Pathol 1997;21:1023–9.
    OpenUrlCrossRefPubMed
  42. ↵
    1. Vicari JJ,
    2. Peek RM,
    3. Falk GW,
    4. et al
    . The seroprevalence of cagA-positive Helicobacter pylori strains in the spectrum of gastroesophageal reflux disease. Gastroenterology 1998;115:50–7.
    OpenUrlCrossRefPubMed
  43. ↵
    1. Vieth M,
    2. Masoud B,
    3. Meining A,
    4. Stolte M
    . Helicobacter pylori infection: protection against Barrett's mucosa and neoplasia?. Digestion 2000;62:225–31.
    OpenUrlCrossRefPubMed
  44. ↵
    1. Wang KX,
    2. Wang XF,
    3. Peng JL,
    4. Cui YB,
    5. Wang J,
    6. Li CP
    . Detection of serum anti-Helicobacter pylori immunoglobulin G in patients with different digestive malignant tumors. World J Gastroenterol 2003;9:2501–4.
    OpenUrlPubMed
  45. ↵
    1. Wang Z,
    2. Tang L,
    3. Sun G,
    4. et al
    . Etiological study of esophageal squamous cell carcinoma in an endemic region: a population-based case control study in Huaian, China. BMC Cancer 2006;6:287.
    OpenUrlCrossRefPubMed
  46. ↵
    1. Weston AP,
    2. Badr AS,
    3. Topalovski M,
    4. Cherian R,
    5. Dixon A,
    6. Hassanein RS
    . Prospective evaluation of the prevalence of gastric Helicobacter pylori infection in patients with GERD, Barrett's esophagus, Barrett's dysplasia, and Barrett's adenocarcinoma. Am J Gastroenterol 2000;95:387–94.
    OpenUrlCrossRefPubMed
  47. ↵
    1. Wright TA,
    2. Myskow M,
    3. Kingsnorth AN
    . Helicobacter pylori colonization of Barrett's esophagus and its progression to cancer. Dis Esophagus 1997;10:196–200.
    OpenUrlPubMed
  48. ↵
    1. Wu AH,
    2. Crabtree JE,
    3. Bernstein L,
    4. et al
    . Role of Helicobacter pylori CagA+ strains and risk of adenocarcinoma of the stomach and esophagus. Int J Cancer 2003;103:815–21.
    OpenUrlCrossRefPubMed
  49. ↵
    1. Wu AH,
    2. Tseng CC,
    3. Hankin J,
    4. Bernstein L
    . Fiber intake and risk of adenocarcinomas of the esophagus and stomach. Cancer Causes Control 2007;18:713–22.
    OpenUrlCrossRefPubMed
  50. ↵
    1. Wu DC,
    2. Wu IC,
    3. Lee JM,
    4. et al
    . Helicobacter pylori infection: a protective factor for esophageal squamous cell carcinoma in a Taiwanese population. Am J Gastroenterol 2005;100:588–93.
    OpenUrlCrossRefPubMed
  51. ↵
    1. Ye W,
    2. Held M,
    3. Lagergren J,
    4. et al
    . Helicobacter pylori infection and gastric atrophy: risk of adenocarcinoma and squamous-cell carcinoma of the esophagus and adenocarcinoma of the gastric cardia. J Natl Cancer Inst 2004;96:388–96.
    OpenUrlAbstract/FREE Full Text
  52. ↵
    1. Romero-Gallo J,
    2. Perez-Perez GI,
    3. Novick RP,
    4. Kamath P,
    5. Norbu T,
    6. Blaser MJ
    . Responses of endoscopy patients in Ladakh, India, to Helicobacter pylori whole-cell and Cag A antigens. Clin Diagn Lab Immunol 2002;9:1313–7.
    OpenUrlCrossRefPubMed
  53. ↵
    1. Moayyedi P
    . Meta-analysis: can we mix apples and oranges?. Am J Gastroenterol 2004;99:2297–301.
    OpenUrlCrossRefPubMed
  54. ↵
    1. Sterne JA,
    2. Egger M,
    3. Davey Smith G
    . Systematic reviews in health care: Investigating and dealing with publication and other biases in meta-analysis. BMJ 2001;323:101–5.
    OpenUrlFREE Full Text
  55. ↵
    1. Begg CB,
    2. Mazumdar M
    . Operating characteristics of a rank correlation test for publication bias. Biometrics 1994;50:1088–101.
    OpenUrlCrossRefPubMed
  56. ↵
    1. Egger M,
    2. Davey Smith G,
    3. Schneider M,
    4. Minder C
    . Bias in meta-analysis detected by a simple, graphical test. BMJ 1997;315:629–34.
    OpenUrlAbstract/FREE Full Text
  57. ↵
    1. Higgins JP,
    2. Thompson SG,
    3. Deeks JJ,
    4. Altman DG
    . Measuring inconsistency in meta-analyses. BMJ 2003;327:557–60.
    OpenUrlFREE Full Text
  58. ↵
    1. Falush D,
    2. Wirth T,
    3. Linz B,
    4. et al
    . Traces of human migrations in Helicobacter pylori populations. Science 2003;299:1582–5.
    OpenUrlAbstract/FREE Full Text
  59. ↵
    1. Blaser MJ
    . Who are we? Indigenous microbes and the ecology of human diseases. EMBO Rep 2006;7:956–60.
    OpenUrlCrossRefPubMed
  60. ↵
    1. Everhart JE,
    2. Kruszon-Moran D,
    3. Perez-Perez GI,
    4. Tralka TS,
    5. McQuillan G
    . Seroprevalence and ethnic differences in Helicobacter pylori infection among adults in the United States. J Infect Dis 2000;181:1359–63.
    OpenUrlAbstract/FREE Full Text
  61. ↵
    1. Chen Y,
    2. Blaser MJ
    . Helicobacter pylori colonization is inversely associated with childhood asthma. J Infect Dis 2008;198:553–60.
    OpenUrlCrossRefPubMed
  62. ↵
    1. Malaty HM,
    2. El-Kasabany A,
    3. Graham DY,
    4. et al
    . Age at acquisition of Helicobacter pylori infection: a follow-up study from infancy to adulthood. Lancet 2002;359:931–5.
    OpenUrlCrossRefPubMed
  63. ↵
    1. Banatvala N,
    2. Mayo K,
    3. Megraud F,
    4. Jennings R,
    5. Deeks JJ,
    6. Feldman RA
    . The cohort effect and Helicobacter pylori. J Infect Dis 1993;168:219–21.
    OpenUrlAbstract/FREE Full Text
  64. ↵
    Helicobacter and Cancer Collaborative Group. Gastric cancer and Helicobacter pylori: a combined analysis of 12 case control studies nested within prospective cohorts. Gut 2001;49:347–53.
    OpenUrlAbstract/FREE Full Text
  65. ↵
    1. Devesa SS,
    2. Blot WJ,
    3. Fraumeni JF Jr.
    . Changing patterns in the incidence of esophageal and gastric carcinoma in the United States. Cancer 1998;83:2049–53.
    OpenUrlCrossRefPubMed
  66. ↵
    1. Kamangar F,
    2. Dawsey SM,
    3. Blaser MJ,
    4. et al
    . Opposing risks of gastric cardia and noncardia gastric adenocarcinomas associated with Helicobacter pylori seropositivity. J Natl Cancer Inst 2006;98:1445–52.
    OpenUrlAbstract/FREE Full Text
  67. ↵
    1. Dawsey SM,
    2. Mark SD,
    3. Taylor PR,
    4. Limburg PJ
    . Gastric cancer and H. pylori. Gut 2002;51:457–8.
    OpenUrlFREE Full Text
  68. ↵
    1. Wren AM,
    2. Bloom SR
    . Gut hormones and appetite control. Gastroenterology 2007;132:2116–30.
    OpenUrlCrossRefPubMed
  69. ↵
    1. Whiteman DC,
    2. Sadeghi S,
    3. Pandeya N,
    4. et al
    . Combined effects of obesity, acid reflux and smoking on the risk of adenocarcinomas of the oesophagus. Gut 2007;57:173–80.
    OpenUrlCrossRefPubMed
  70. ↵
    1. Blaser MJ,
    2. Chen Y,
    3. Reibman J
    . Does Helicobacter pylori protect against asthma and allergy? Gut 2008;57:561–7.
    OpenUrlFREE Full Text
  71. ↵
    1. Chen Y,
    2. Blaser MJ
    . Inverse associations of Helicobacter pylori with asthma and allergy. Arch Intern Med 2007;167:821–7.
    OpenUrlCrossRefPubMed
  72. ↵
    1. Blaser MJ
    . An endangered species in the stomach. Sci Am 2005;292:38–45.
    OpenUrlPubMed
  73. ↵
    1. Lagergren J,
    2. Bergstrom R,
    3. Lindgren A,
    4. Nyren O
    . Symptomatic gastroesophageal reflux as a risk factor for esophageal adenocarcinoma. N Engl J Med 1999;340:825–31.
    OpenUrlCrossRefPubMed
  74. ↵
    1. Perez-Perez GI,
    2. Salomaa A,
    3. Kosunen TU,
    4. et al
    . Evidence that cagA(+) Helicobacter pylori strains are disappearing more rapidly than cagA(−) strains. Gut 2002;50:295–8.
    OpenUrlAbstract/FREE Full Text
  75. ↵
    1. Blaser MJ,
    2. Berg DE
    . Helicobacter pylori genetic diversity and risk of human disease. J Clin Invest 2001;107:767–73.
    OpenUrlCrossRefPubMed
  76. ↵
    1. Figueiredo C,
    2. Machado JC,
    3. Pharoah P,
    4. et al
    . Helicobacter pylori and interleukin 1 genotyping: an opportunity to identify high-risk individuals for gastric carcinoma. J Natl Cancer Inst 2002;94:1680–7.
    OpenUrlAbstract/FREE Full Text
  77. ↵
    1. Rokkas T,
    2. Pistiolas D,
    3. Sechopoulos P,
    4. Robotis I,
    5. Margantinis G
    . Relationship between Helicobacter pylori infection and esophageal neoplasia: a meta-analysis. Clin Gastroenterol Hepatol 2007;5:1413–7.
    OpenUrlCrossRefPubMed
  78. ↵
    1. Shapiro S
    . Meta-analysis/Sh meta-analysis. Am J Epidemiol 1994;140:771–8.
    OpenUrlAbstract/FREE Full Text
  79. ↵
    1. Egger M,
    2. Schneider M,
    3. Davey Smith G
    . Spurious precision? Meta-analysis of observational studies. BMJ 1998;316:140–4.
    OpenUrlFREE Full Text
PreviousNext
Back to top
Cancer Prevention Research: 1 (5)
October 2008
Volume 1, Issue 5
  • Table of Contents
  • Table of Contents (PDF)
  • About the Cover

Sign up for alerts

View this article with LENS

Open full page PDF
Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for sharing this Cancer Prevention Research article.

NOTE: We request your email address only to inform the recipient that it was you who recommended this article, and that it is not junk mail. We do not retain these email addresses.

Enter multiple addresses on separate lines or separate them with commas.
Helicobacter pylori and Esophageal Cancer Risk: A Meta-analysis
(Your Name) has forwarded a page to you from Cancer Prevention Research
(Your Name) thought you would be interested in this article in Cancer Prevention Research.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Helicobacter pylori and Esophageal Cancer Risk: A Meta-analysis
Farhad Islami and Farin Kamangar
Cancer Prev Res October 1 2008 (1) (5) 329-338; DOI: 10.1158/1940-6207.CAPR-08-0109

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Share
Helicobacter pylori and Esophageal Cancer Risk: A Meta-analysis
Farhad Islami and Farin Kamangar
Cancer Prev Res October 1 2008 (1) (5) 329-338; DOI: 10.1158/1940-6207.CAPR-08-0109
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
    • Abstract
    • Materials and Methods
    • Results
    • Discussion
    • Disclosure of Potential Conflicts of Interest
    • Acknowledgments
    • Footnotes
    • References
  • Figures & Data
  • Info & Metrics
  • PDF
Advertisement

Related Articles

Cited By...

More in this TOC Section

  • Vitamin D and Mammographic Breast Density
  • Polyphenon E for Prevention of Colorectal Cancer
  • Dopamine and skin tumorigenesis
Show more Research Articles
  • Home
  • Alerts
  • Feedback
  • Privacy Policy
Facebook   Twitter   LinkedIn   YouTube   RSS

Articles

  • Online First
  • Current Issue
  • Past Issues

Info for

  • Authors
  • Subscribers
  • Advertisers
  • Librarians

About Cancer Prevention Research

  • About the Journal
  • Editorial Board
  • Permissions
  • Submit a Manuscript
AACR logo

Copyright © 2021 by the American Association for Cancer Research.

Cancer Prevention Research
eISSN: 1940-6215
ISSN: 1940-6207

Advertisement