Severe atrophic gastritis with Helicobacter pylori infection and gastric cancer

Background. We conducted a case-control study to evaluate whether patients with severe gastric atrophy (indicated by serum pepsinogen concentration) have a high risk of gastric cancer. Methods. At the time of diagnosis of gastric cancer, sera from 301 patients (cases) and 602 sex- and age-matched cancer-free individuals (controls) were tested for the presence of anti-Helicobacter pylori IgG antibody (HM-CAP enzyme-linked immunoassay [ELISA] kit; Kyowa Medix, Tokyo, Japan) and serum pepsinogen (PG) levels (PG I and II Riabead Kits; Dainabot, Tokyo, Japan). We defined positivity for pepsinogen a pepsinogen I concentration of less than 70 ng/mL and a PG I/II ratio of less than 3.0. We categorized the subjects according to serum pepsinogen levels and anti-Helicobacter pylori IgG antibody, creating four categories. Results. Of the 301 cancer cases, 177 had positive serum pepsinogen levels, and 172 were positive for anti-Helicobacter pylori IgG antibody. The category in which subjects had positive serum pepsinogen levels and were negative for anti-Helicobacter pylori IgG antibody had the highest proportion (76.9%) of individuals with gastric cancer and the highest odds ratio (4.20) of the four categories. The odds ratios were 2.55 (95% confidence interval; 1.92–3.88) for positive serum pepsinogen levels and 0.93 (95% confidence interval; 0.63–1.27) for positive anti-Helicobacter pylori IgG antibody. Conclusion. These results suggest that patients with positive serum pepsinogen levels who are negative for IgG antibody to Helicobacter pylori, constitute a high-risk group for gastric cancer. Helicobacter pylori infection is associated with the development of gastric cancer by providing a suitable environment i.e., severe gastric atrophy, for carcinogenesis of the gastric mucosa. Received for publication on Mar. 20, 1998; accepted on Aug. 20, 1998     

Progression of chronic atrophic gastritis associated with Helicobacter pylori infection increases risk of gastric cancer

We conducted a longitudinal cohort study to determine the association of Helicobacter pylori infection and the progression of chronic atrophic gastritis (CAG) with gastric cancer. A cohort of 4655 healthy asymptomatic subjects was followed for a mean period of 7.7 years. H. pylori infection was established by serum specific antibodies and the presence of CAG was confirmed by serum pepsinogen. During the follow-up period, 45 gastric cancer cases were detected (incidence rate, 126/100000 person-years). A univariate analysis after adjustment for age showed that both H. pylori and CAG were significantly associated with gastric cancer. To clarify the interaction between H. pylori and CAG, an analysis stratified by H. pylori- and CAG-status was performed. No cancer developed in the H. pylori(-)/CAG(-) group during the study period. This supports the theory that it is quite rare for any type of gastric cancer to develop in an H. pylori-free healthy stomach. With the progression of H. pylori-induced gastritis, the risk of gastric cancer increased in a stepwise fashion from CAG-free gastritis [H. pylori(+)/CAG(-) group] (HR=7.13, 95%CI=0.95-53.33) to CAG [H. pylori(+)/CAG(+) group] (HR=14.85, 95%CI=1.96-107.7) and finally to severe CAG with extensive intestinal metaplasia [H. pylori(-)/CAG(+) group] (HR=61.85, 95%CI=5.6-682.64) in which loss of H. pylori from the stomach is observed. Therefore, it is probable that H. pylori alone is not directly associated with stomach carcinogenesis. Instead, H. pylori appears to influence stomach carcinogenesis through the development of CAG. The observed positive correlation between the extent of H. pylori-induced gastritis and the development of cancer was strong, especially for the intestinal type. These results are compelling evidence that severe gastritis with extensive intestinal metaplasia is a major risk factor for gastric cancer, and they confirm the previously described model of stomach carcinogenesis: the gastritis-metaplasia-carcinoma sequence.     

Association of Helicobacter pylori infection with chronic atrophic gastritis: Meta-analyses according to type of disease definition

Helicobacter pylori is a major risk factor for chronic atrophic gastritis (CAG). A large variety of definitions of CAG have been used in epidemiologic studies in the past. The aim of this work was to systematically review and summarize estimates of the association between H. pylori infection and CAG according to the various definitions of CAG. Articles on the association between H. pylori infection and CAG published until July 2007 were identified. Separate meta-analyses were carried out for studies defining CAG based on gastroscopy with biopsy, serum pepsinogen I (PG I) only, the pepsinogen I/pepsinogen II ratio (PG I/PG II ratio) only, or a combination of PG I and the PG I/PG II ratio. Numbers of identified studies and summary odds ratios (OR) (95% confidence intervals) were as follows: gastroscopy with biopsy: n = 34, OR = 6.4 (4.0-10.1); PG I only: n = 13, OR = 0.9 (0.7-1.2); PG I/PG II ratio: n = 8, OR = 7.2 (3.1-16.8); combination of PG I and the PG I/PG II ratio: n = 20, OR = 5.7 (4.4-7.5). Studies with CAG definitions based on gastroscopy with biopsy or the PG I/PG II ratio (alone or in combination with PG I) yield similarly strong associations of H. pylori with CAG. The association is missed entirely in studies where CAG is defined by PG I only.     

Helicobacter pylori infection,chronic atrophic gastritis and risk of stomach and esophagus cancer: Results from the prospective population-based ESTHER cohort study

Helicobacter pylori (H. pylori) infection is considered as principal cause of gastric cancer. It is further associated with a reduced risk of esophageal adenocarcinomas. In a large prospective population-based cohort study including 9,949 subjects with average observation time of 13.8 years, we assessed the risk of invasive gastric and esophageal cancer according to H. pylori infection and presence of chronic atrophic gastritis (CAG). Incidence rates and hazard ratios (HR) derived by Cox proportional hazards models and adjusted for relevant confounders were derived by seroprevalence of H. pylori and cytotoxin-associated gene A (CagA) antibodies and presence of CAG based on serological markers at baseline, respectively. During follow-up, 30 cases of noncardia gastric cancer and 33 cases of esophageal cancer were observed. Infection by H. pylori without and with expression of CagA was associated with a 5.2-fold (95% confidence interval 1.00–27.1) and an 18.2-fold (4.3–77.4) increase of noncardia gastric cancer incidence. A 0.65-fold decreased risk of esophageal adenocarcinomas (HR 0.35, 0.12–0.97) was observed among H. pylori-infected individuals. In participants infected with CagA expressed H. pylori, the presence of mild/moderate and severe CAG was associated with a 6.4-fold (1.3–31.0) and an 11.8-fold (3.1–45.4) increase of gastric cancer incidence, respectively. The results of this prospective population-based cohort study may contribute relevant evidence to the ongoing research of H. pylori-related cancers. The results may furthermore enhance the empirical basis for risk stratification among H. pylori-infected people and for recommendations regarding H. pylori screening and treatment among older adults in a Western population.     

Cancer development based on chronic active gastritis and resulting gastric atrophy as assessed by serum levels of pepsinogen and Helicobacter pylori antibody titer

Our study investigated the relationship between gastric cancer development and activity of Helicobacter pylori‐associated chronic gastritis or the resulting chronic atrophic gastritis (CAG). A cohort of 4,655 healthy asymptomatic subjects, in whom serum pepsinogen (PG) and H. pylori antibody titer had been measured to assess the activity and stage of H. pylori‐associated chronic gastritis, was followed for up to 16 years, and cancer development was investigated. In subjects with a serologically diagnosed healthy stomach (H. pylori‐negative/CAG‐negative), cancer incidence rate was low, at 16/100,000 person‐years. With the establishment of H. pylori infection and progression of chronic gastritis, significant stepwise cancer risk elevations were seen from CAG‐free subjects (H. pylori‐positive/CAG‐negative) [hazard ratio (HR) = 8.9, 95% confidence interval (CI) = 2.7–54.7] to subjects with CAG (H. pylori‐positive/CAG‐positive) (HR = 17.7, 95% CI = 5.4–108.6) and finally to subjects with metaplastic gastritis (H. pylori‐negative/CAG‐positive) (HR = 69.7, 95% CI = 13.6–502.9). In H. pylori‐infected CAG‐free subjects, significantly elevated cancer risk was observed in the subgroup with active inflammation‐based high PG II level or potent immune response‐based high H. pylori antibody titer; the former was associated with a particularly high risk of diffuse‐type cancer, and both subgroups showed high cancer incidence rates of around 250/100,000 person‐years, comparable to that in subjects with CAG. No such risk elevation was observed in H. pylori‐infected subjects with CAG. These results clearly indicate that gastric cancer develops mainly from the gastritis‐atrophy‐metaplasia‐cancer sequence and partly from active inflammation‐based direct carcinogenesis, and that serum levels of PG and H. pylori antibody titer provide indices of cancer development in H. pylori‐infected subjects.     

Pepsinogen A,pepsinogen C,and gastrin as markers of atrophic chronic gastritis in European dyspeptics

Serum levels of pepsinogen and gastrin are parameters that can be used as biomarkers for gastric mucosa. The aim of this study was to validate these serum biomarkers, that is pepsinogen A (PGA), pepsinogen C (PGC), PGA/PGC ratio, and gastrin, as screening tests for precancerous lesions: atrophic chronic gastritis (ACG) or Helicobacter pylori-related corpus-predominant or multifocal atrophy. The study population was comprised of a subsample of 284 patients from the 451 included in the Eurohepygast cohort, between 1995 and 1997. The concentrations of PGA, PGC, and gastrin were measured by radioimmunoassays. Histological diagnosis was the gold standard. Cut-off points were calculated using receiving operator characteristics (ROC) curves. Factors linked to variation of biomarkers were identified using multivariate linear regression. The mean of each biomarker in the sample was: PGA, 77.4 microg x l(-1); PGC, 13.2 microg x l(-1); PGA/PGC, 6.7; and gastrin, 62.4 ng x l(-1). For ACG patients, the areas under the PGA, PGC, PGA/PGC, and gastrin ROC curves were 0.55, 0.62, 0.73, and 0.58, respectively. The best cut-off point for PGA/PGC was 5.6, with sensitivity 65% and specificity 77.9%. For H. pylori-related corpus-predominant or multifocal atrophy, the areas under the respective ROC curves were 0.57, 0.67, 0.84, and 0.69. The best cut-off point for PGA/PGC was 4.7, with sensitivity 77.1% and specificity 87.4%. The results suggested that only the PGA/PGC ratio can be considered as a biomarker for precancerous lesions of the stomach, and may be useful as a screening test.     

Helicobacter pylori,dietary factors,and atrophic gastritis in five Japanese populations with different gastric cancer mortality

In a cross-sectional study of 634 men aged 40 to 49 years, randomly selected from five areas of Japan with different rates of gastric cancer mortality, 121 men of 624 evaluated were diagnosed as having atrophic gastritis through serum pepsinogen I<70 ng/ml and the pepsinogen I (PGI)/pepsinogen II (PGII) ratio <3.0. We examined the relation of Helicobacter pylori (H. pylori) antibodies and dietary factors, including plasma level of antioxidant micronutrients, to the presence of atrophic gastritis. Presence of H. pylori IgG antibodies was associated with increased risk of atrophic gastritis (odds ratio [OR]=1.9, 95 percent confidence interval [CI]=1.1–3.3). As the level of plasma -carotene increased, we found a steady decrease in the risk of atrophic gastritis (OR for second quartile = 0.7, third quartile = 0.6, fourth quartile = 0.4, with CI=0.2–0.8). Frequent intake of yellow vegetables also was associated with lower risk, while frequent intake of soybean products was related to increased risk. Although H. pylori antibodies, -carotene level, and intake of soybean products were all significant in the multivariate analysis, these factors did not explain the differences in atrophic gastritis prevalence among the five regions. The analysis of these risk factors in relation to each pepsinogen marker showed that although both H. pylori infection and low plasma -carotene were associated with the decreased level of serum PGI/II ratio, the former was derived from the increase of PGII, which is common in early stage of atrophic gastritis, and the latter from the decrease of PGI, which is specific to severe atrophic gastritis. This finding suggests that H. pylori infection is associated with the formation of atrophic gastritis, while -carotene protects its advancement as well as formation.This study was supported in part by grants-in-aid for Cancer Research from the Ministry of Health and Welfare and for Scientific Research from the Ministry of Education, Science and Culture of Japan.     

Incidence and risk factors for the development of chronic atrophic gastritis: Five year follow‐up of a population‐based cohort study

Chronic atrophic gastritis (CAG) is a well‐established precursor of intestinal gastric cancer. However, data on incidence of CAG are rare, especially from population‐based studies. The aim of this analysis was to estimate the incidence of CAG in a large population‐based study among older adults from Germany and to identify major risk factors associated with its development. In the baseline and 5‐year follow‐up examinations of the ESTHER study, serological measurements of pepsinogen (PG) I and II and Helicobacter pylori antibodies were performed in 5,229 women and men, aged 50–74 years at baseline. Information on additional potential risk factors was obtained by questionnaire. CAG was defined by PGI < 70 ng/mL and PGI/PGII < 3. In total, there were 58 (1.1%) incident CAG cases. CAG incidence increased with increasing age from 0.5% in age group 50–54 years to 2.1% in age group 70–74 years. Seropositivity with H. pylori was strongly associated with CAG incidence, with adjusted odds ratios of 5.0 [95% confidence interval (CI): 1.6–15.8] and 11.3 (95% CI: 4.2–30.0) for participants with cytotoxin associated gene A (cagA) negative and cagA positive H. pylori infection at both baseline and follow‐up compared to those without H. pylori infection, respectively. Gender, education, smoking, alcohol consumption and family history of gastric cancer were not significantly associated with CAG incidence. Incidence of CAG is rather low in the German population. Older age and infection with H. pylori are key risk factors for the development of CAG.     

CagA+ Helicobacter pylori infection and gastric cancer risk in the EPIC-EURGAST study

Helicobacter pylori (H. pylori), atrophic gastritis, dietary and life-style factors have been associated with gastric cancer (GC). These factors have been evaluated in a large case-control study nested in the European Prospective Investigation into Cancer and Nutrition carried out in 9 countries, including the Mediterranean area. Participants, enrolled in 1992-1998, provided life-style and dietary information and a blood sample (360,000; mean follow-up: 6.1 years). For 233 GC cases diagnosed after enrolment and their 910 controls individually-matched by center, gender, age and blood donation date H. pylori antibodies (antilysate and antiCagA) and plasma Pepsinogen A (PGA) were measured by ELISA methods. Severe chronic atrophic gastritis (SCAG) was defined as PGA circulating levels <22 microg/l. Overall, in a conditional logistic regression analysis adjusted for education, smoke, weight and consumption of total vegetables, fruit, red and preserved meat, H. pylori seropositivity was associated with GC risk. Subjects showing only antibodies anti-H. pylori lysate, however, were not at increased risk, while those with antiCagA antibodies had a 3.4-fold increased risk. Overall, the odds ratio associated with SCAG was 3.3 (95% CI 2.2-5.2). According to site, the risk of noncardia GC associated with CagA seropositivity showed a further increase (OR 6.5; 95% CI 3.3-12.6); on the other hand, a ten-fold increased risk of cardia GC was associated with SCAG (OR 11.0; 95% CI 3.0-40.9). These results support the causal relationship between H. pylori CagA+ strains infection, and GC in these European populations even after taking into account dietary habits. This association was limited to distal GC, while serologically defined SCAG was strongly associated with cardia GC, thus suggesting a divergent risk pattern for these 2 sites.     

Risk of gastric cancer in asymptomatic, middle-aged Japanese subjects based on serum pepsinogen and Helicobacter pylori antibody levels

A total of 5,209 asymptomatic, middle-aged subjects, whose serum pepsinogen (PG) and Helicobacter pylori antibody levels had been assessed, were followed for 10 years. Subjects with positive serum H. pylori antibodies (>50 U/mL) had an increased cancer risk (HR = 3.48, 95% CI = 1.26-9.64). Risk of gastric cancer increased as the antibody level increased; the H. pylori-positive group with antibody levels >500 U/mL had the highest incidence rate (325/100,000 person-years). Cancer development also increased with a reduced serum PG I level or a reduced PG I/II ratio; the risk was significantly elevated with serum PG I level or=30 ng/mL (HR = 3.81, 95% CI = 1.10-13.21). Using H. pylori antibody and PG levels, subgroups with an especially high or low cancer incidence rate could be identified. H. pylori-negative or indeterminate subjects with low PG level (PG I 500 U/mL and a low PG level were among the subgroups with a high cancer incidence rate (over 400/100,000 person-years). In contrast, H. pylori-negative subjects with a PG I level >70 ng/mL or a PG I/II ratio >3.0 had the lowest risk; none of these subjects developed cancer. Thus, serum PG levels and/or H. pylori antibody levels can be used to predict the risk of cancer in individuals with H. pylori-related gastritis from the general population.     

Community-based familial study of Helicobacter pylori infection among healthy Japanese Brazilians

Background

The present study of Helicobacter pylori infection was conducted in family units of Japanese Brazilians living in São Paulo city. The authors attempted to determine the seroprevalence of H. pylori infection within family units of Japanese Brazilians and to identify risk factors associated with intrafamilial transmission.

Methods

The seroprevalence was determined in 1037 healthy and asymptomatic volunteer subjects aged 0–69 years (530 adults and 507 children) of 265 families. Demographic data and details of living conditions were obtained from each family.

Results

H. pylori seropositive infection was found in 39.2% of the parents and 9.3% of the children. A reduced risk of H. pylori infection was found for girls (odds ratio [OR] 0.45; 95% confidence interval [CI], 0.23–0.86). The prevalence of infection was 3.5% for children with uninfected parents; 9.9% (OR, 2.51; 95% CI, 0.95–6.61) for those with a seronegative mother and a seropositive father; 14.9% (OR, 4.93; 95% CI, 1.86–13.06) for those with a seropositive mother and a seronegative father; and 16.0% (OR, 5.29; 95% CI, 1.98–14.14) for those with seropositive parents. On multivariate analysis, the use of a pacifier, and mother's symptoms of nausea and vomiting were significantly associated with the risk of H. pylori infection for children, and the child having her/his own room was significantly associated with a reduced risk. Income was not associated with H. pylori infection in children and was inversely associated in parents.

Conclusion

The prevalence of H. pylori infection in family units of Japanese Brazilians supports the hypothesis of a predominant role for mother–child transmission of H. pylori infection, mainly through contact with regurgitated gastric juice in the mother's mouth.     

Correlation between the prevalence of gastritis and gastric cancer in Japan

To verify the hypothesis that chronic atrophic gastritis (CAG) is a precancerous lesion for gastric cancer, we investigated the correlation between the prevalence rates for CAG determined by levels of serum pepsinogens (I and II) of randomly selected, healthy, blood donors and the mortality rates for gastric cancer among four prefectures (Akita, Iwate, Miyagi, and Okinawa) in Japan. The prevalence rates for CAG according to a criterion that the level of pepsinogen I is below 70 ng/ml and the pepsinogen I to pepsinogen II ratio is below 3.0, were the highest in Akita for both sexes (38.8 percent in males, 37.8 percent in females) and the lowest in Okinawa (13.9 percent in males, 12.3 percent in females), where mortality rates for gastric cancer are the highest and the lowest in Japan, respectively. The correlation between the prevalence rates for CAG and the standardized mortality ratios for gastric cancer among these four prefectures was statistically significant in males (r=0.97, P=0.03), but less significant in females (r=0.92, P=0.08). These data strongly support the hypothesis that CAG is a precancerous lesion. The limitations of our cross-sectional study and the advantages of measuring the levels of serum pepsinogens in epidemiologic studies and in mass-screening programs for gastric cancer are discussed.Drs Fukao and Hisamichi are with the Toboku University School of Medicine, Sendai, Japan. Dr Obsato is with the Akita Blood Center. Dr Fujino is with the Iwate Blood Center. Dr Endo is with the Miyagi Blood Center. Dr Iha is with the Okinawa Blood Center, Japan. Address correspondence to Dr Fukao, Department of Public Health, Toboku University School of Medicine, 2-1, Seiryomachi, Aobaku, Sendai, 980 Japan. This work was supported in part by a Grant-in-Aid for Cancer Research from The Ministry of Education, Science and Culture of Japan.     

Elevated risk of colorectal adenoma with Helicobacter pylori-related chronic gastritis: a population-based case-control study

This study investigated correlations between Helicobacter pylori infection or chronic atrophic gastritis (CAG) and risk of colorectal adenoma in a population-based case-control study. Subjects comprised asymptomatic, middle-aged, male Japanese factory workers who participated in an annual health check-up program, including cancer screening with colonoscopy. We selected 239 colorectal adenoma cases based on histological evaluation and 239 age-matched adenoma-free controls, and evaluated colorectal adenoma risk according to stage of H. pylori-related chronic gastritis as determined by serum tests for H. pylori antibody titer and pepsinogen. Subjects with colorectal adenoma were more likely to be smokers and have hypercholesterolemia. H. pylori infection was a risk factor for adenoma as a whole (crude odds ratio [OR]: 2.26, 95% confidence interval [CI]: 1.44-3.55). Analysis of distal adenoma cases showed that adenoma risk was significantly increased in the presence of H. pylori infection, but there was no further increase in risk with CAG. In contrast, proximal adenoma risk increased stepwise with the presence and progression of H. pylori-related chronic gastritis and showed a maximal and significant increase with CAG (crude OR: 4.51, 95% CI: 1.43-14.2). Subjects with more extensive and severe gastritis showed still higher risk not only for proximal but also for distal adenoma. H. pylori-related chronic gastritis is likely to be involved in the development of colorectal neoplasms, and its progression appears to increase the risk, particularly for proximal adenomas. Knowing the H. pylori-related chronic gastritis stage will probably be useful for evaluation of risk for colorectal neoplasia.     

Alcohol consumption and chronic atrophic gastritis: Population‐based study among 9,444 older adults from Germany

Moderate alcohol consumption has been suggested to facilitate elimination of Helicobacter pylori infection which is a key risk factor for chronic atrophic gastritis (CAG) and gastric cancer. The aim of our study was to assess the association of alcohol consumption with CAG among older adults from Germany. In the baseline examination of ESTHER, a population‐based study conducted in Saarland, serological measurements of pepsinogen I and II (for CAG definition) and H. pylori antibodies were taken in 9,444 subjects aged 50–74 years. Moderate current (<60 g/week) and lifetime (≤51,376 g, lowest quartile) alcohol consumption were found to be associated with significantly reduced CAG risk compared to alcohol abstinence with adjusted odds ratios of 0.71 (0.55–0.90) and 0.73 (0.55–0.96), respectively. Inverse associations with CAG were observed for moderate alcohol consumption from both beer and wine, and were slightly attenuated after additional adjustment for H. pylori infection. Our results are consistent with the hypothesis that moderate alcohol consumption may be inversely related to CAG, partly through facilitating the elimination of H. pylori. However, the observed patterns suggest that other mechanisms are likely to contribute to the association as well. © 2009 UICC     

Role of Helicobacter pylori infection and chronic inflammation in gastric cancer in the cardia

BACKGROUND: Helicobacter pylori-induced gastritis is an important factor for gastric carcinogenesis. However, it is still controversial whether it is also applicable for cardiac cancer development. Recently, we reported that H. pylori is an important factor for the induction of cardiac inflammation. We examined the status of H. pylori-induced gastritis in patients with cardiac cancer. METHODS: Seventy-five Japanese patients (58 men; mean age, 64.2 years) with cardiac cancer were studied. Cardiac cancer was defined as that mainly located within 2 cm from the squamo-columnar junction (SCJ). Histological gastritis including the cardiac region was evaluated using the biopsy or surgically resected sections. Cardiac inflammation was evaluated at 1 cm distal from SCJ in lesser curvature. Sera were collected and several markers were evaluated. The status of H. pylori infection was evaluated by histology and serum antibodies. Expressions of cytokeratins were examined by immunohistochemical analysis. RESULTS: Out of 75 patients with cardiac cancer, H. pylori was positive in 71 (95%) patients. The cardiac inflammation was examined in 30 patients (26 with H. pylori and four without H. pylori infection) and we found cardiac inflammation was present in all cases with H. pylori infection. Histologically, H. pylori-related gastritis was also found in the gastric corpus and antrum. Serological data were consistent with the presence of chronic atrophic gastritis. Intestinal metaplasia was found in 18 cases in the cardiac mucosa, and their cytokeratin 7/20 pattern was judged as a gastric pattern in all cases. CONCLUSION: H. pylori infection is closely associated with cardiac cancer.     

CagA-producing Helicobacter pylori and increased risk of gastric cancer: a nested case-control study in Korea

In a nested-case control study of 100 cases of gastric cancer and 400 matched controls in relation to virulence factors of Helicobacter pylori in a Korean cohort, CagA seropositivity was significantly associated with a higher risk of gastric cancer among H. pylori-infected subjects (OR=3.57, 95% CI 1.05-12.14).     

Helicobacter pylori and oesophageal and gastric cancers in a prospective study in China

In a cohort of 29,584 residents of Linxian, China, followed from 1985 to 2001, we conducted a case-cohort study of the magnitude of the association of Helicobacter pylori seropositivity with cancer risk in a random sample of 300 oesophageal squamous cell carcinomas, 600 gastric cardia adenocarcinomas, all 363 diagnosed gastric non-cardia adenocarcinomas, and a random sample of the entire cohort (N=1050). Baseline serum was evaluated for IgG antibodies to whole-cell and CagA H. pylori antigens by enzyme-linked immunosorbent assay. Risks of both gastric cardia and non-cardia cancers were increased in individuals exposed to H. pylori (Hazard ratios (HRs) and 95% confidence intervals=1.64; 1.26-2.14, and 1.60; 1.15-2.21, respectively), whereas risk of oesophageal squamous cell cancer was not affected (1.17; 0.88-1.57). For both cardia and non-cardia cancers, HRs were higher in younger individuals. With longer time between serum collection to cancer diagnosis, associations became stronger for cardia cancers but weaker for non-cardia cancers. CagA positivity did not modify these associations. The associations between H. pylori exposure and gastric cardia and non-cardia adenocarcinoma development were equally strong, in contrast to Western countries, perhaps due to the absence of Barrett's oesophagus and oesophageal adenocarcinomas in Linxian, making all cardia tumours of gastric origin, rather than a mixture of gastric and oesophageal malignancies.     

The influence of cytokine gene polymorphisms on the risk of developing gastric cancer in patients with Helicobacter pylori infection

Background

Helicobacter pylori infection is the main cause of gastric cancer. The disease progression is influenced by the host inflammatory responses, and cytokine single nucleotide polymorphisms (SNPs) may have a role in the course of the disease. The aim of our study was to investigate proinflammatory cytokine polymorphisms, previously associated with the development of gastric cancer, in a Slovenian population.

Patients and methods.

In total 318 patients and controls were selected for the study and divided into three groups: (i) patients with gastric cancer (n = 58), (ii) patients with chronic gastritis (n = 60) and (iii) healthy control group (n = 200). H. pylori infection in patient groups was determined by serology, histology and culture. Four proinflammatory gene polymorphisms were determined (IL-1β, IL-1ra, TNF-α, TLR-4) in all subjects.

Results

We found a statistically significant difference between males and females for the groups (p = 0.025). Odds ratio (OR) for gastric cancer risk for females was 0.557 (95% confidence interval [CI]: 0.233–1.329) and for chronic gastritis 2.073 (95% CI: 1.005–4.277). IL-1B-511*T/T homozygous allele for cancer group had OR = 2.349 (95% CI: 0.583–9.462), heterozygous IL-1B-511*T had OR = 1.470 (95% CI: 0.583–3.709) and heterozygotes in TNF-A-308 genotype for chronic gastritis had OR = 1.402 (95% CI: 0.626–3.139). Other alleles had OR less than 1.

Conclusions

We could not prove association between gastric cancer and chronic gastritis due to H. pylori in any cytokine SNPs studied in Slovenian population. Other SNPs might be responsible besides infection with H. pylori for the progression from atrophy to neoplastic transformation.     

Helicobacter pylori infection predicts favorable outcome in patients with gastric cancer

Background

Recent studies have suggested a controversial role of Helicobacter pylori infection in gastric cancer prognosis. The aim of the present study was to investigate the potential impact of H. pylori status on the prognosis of patients with gastric cancer in a Chinese prospective cohort.

Methods

Between 2007 and 2009, 261 patients with curatively resected gastric cancer were enrolled in the study. H. pylori status was defined by means of immunohistochemical staining in tumour and non-neoplastic tissues. Treatment prognosis was measured in terms of cancer-specific survival and disease-free survival (dfs). Univariate and multivariate Cox regression models were used to assess the association between H. pylori status and patient prognosis.

Results

Positivity for H. pylori infection was observed in 188 of the 261 patients (72.0%). In patients positive for H. pylori, mean cancer-specific survival was 55.2 months [95% confidence interval (ci): 53.4 to 56.9 months] and mean dfs was 53.9 months (95% ci: 51.8 to 56.0 months); the same survivals were, respectively, 45.1 months (95% ci: 42.2 to 47.9 months) and 43.7 months (95% ci: 40.4 to 47.0 months) in patients negative for H. pylori. In univariate analysis, positive H. pylori status was associated with better cancer-specific survival [hazard ratio (hr): 0.486; 95% ci: 0.271 to 0.870; p = 0.015] and dfs (hr: 0.540; 95% ci: 0.307 to 0.950; p = 0.033). In multivariate analysis, H. pylori was an independent prognostic factor for cancer-specific survival (hr: 0.485; 95% ci: 0.265 to 0.889; p = 0.019).

Conclusions

Our study demonstrates that positive H. pylori status is a beneficial prognostic indicator in patients with gastric cancer and might suggest possible therapeutic approaches for gastric cancer. Further research is required to better understand inflammation mechanisms and cancer progression.     

A nested case-control study of the association of Helicobacter pylori infection with gastric adenocarcinoma in Korea

In a nested case-control study of 86 cases of gastric adenocarcinoma in relation to Helicobacter pylori infection in the Korean Multi-center Cancer Cohort, the H. pylori IgG seropositivity was 83.7% and that of the 344 matched controls was 80.8%, with a matched odds ratio for H. pylori infection of 1.06 (95% CI, 0.80-1.40).