Helicobacter pylori infection and gastric cancer: evidence fron a retrospective cohort study and nested case-control study in China

AIM: To explore the association between Helicobacter pylori (Hp) infection and risk of gastric cancer in China. METHODS: Utilizing gastroendoscopic biospsy tissue banks accumulated from1980 to1988 in Shandong, Zhejiang, and Jiangsu, where stomach cancer incidence was high, during stomach cancer screening conducted by Health Science Center of Peking University, School of Medicine of Zhejiang University, and Zhongshan Hospital of Fudan University. Warthin Starry silver staining method was applied to determine H. pyloriinfection status of biopsies collected during gastroendoscopic examination. In the retrospective study, the subjects were divided into two cohorts, the exposure cohort was positive H. pyloriinfection, and the non-exposure cohort was negative. Death from stomach cancer was determined as the outcome of the study. Logistic regression and Cox regression were applied to analyze the association between Helicobacterpyloriinfection and gastric cancer risk. In the nested case-control study, there were 28 deaths from gastric cancer in the fields of Muping, Shandong province, and Zhoushan, Zhejiang provinces. 4 controls were matched to each case on the basis of age (±5 years old), sex, residential place at the same time entered into the study. Conditional logistic regression analysis was used to analyze the data.RESULTS: There were a total of 2 719 subjects (male 1 399,female 1 320) with gastroendoscopic biopsies stored available treated as a cohort. H. pyloripositive cohort included 1 671 subjects (61.5 %) and H. pylorinegative cohort 1 048 subjects(38.5 %). These subjects were followed up for 1-19 years, averaged 10.88 years. The outcome of death from stomach cancer in the exposure cohort was 33, and in the non-exposure cohort 11. After adjustment for age and sex, RR=1.9850 (P=0.0491), 95 % CI was 1.0026, and 3.9301. The results of conditional logistic regression showed an OR of 4.467 and 95 % CI of 1.161, and 17.190 for the nested case control study.CONCLUSION: The results from the retrospective cohort study and the nested-case control study on the association of H. pyloriinfection and gastric cancer in China suggested that Helicobacterpyloriinfection might increase the risk of stomach cancer.     

Helicobacter pylori infection and gastric cancer：evidence from a retrospectiv cohort study and nested case—control study in China

AIM: To explore the association between Helicobacter pylori (Hp) infection and risk of gastric cancer in China. METHODS: Utilizing gastroendoscopic biospsy tissue banks accumulated from 1980 to 1988 in Shandong, Zhejiang, and Jiangsu, where stomach cancer incidence was high, during stomach cancer screening conducted by Health Science Center of Peking University, School of Medicine of Zhejiang University, and Zhongshan Hospital of Fudan University. Warthin Starry silver staining method was applied to determine H. pylori infection status of biopsies collected during gastroendoscopic examination. In the retrospective study, the subjects were divided into two cohorts, the exposure cohort was positive H. pylori infection, and the non-exposure cohort was negative. Death from stomach cancer was determined as the outcome of the study. Logistic regression and Cox regression were applied to analyze the association between Helicobacter pylori infection and gastric cancer risk. In the nested case-control study, there were 28 deaths from gastric cancer in the fields of Muping, Shandong province, and Zhoushan, Zhejiang provinces. 4 controls were matched to each case on the basis of age (+/-5 years old), sex, residential place at the same time entered into the study. Conditional logistic regression analysis was used to analyze the data. RESULTS: There were a total of 2 719 subjects (male 1 399, female 1 320) with gastroendoscopic biopsies stored available treated as a cohort. H. pylori positive cohort included 1 671 subjects (61.5 %) and H. pylori negative cohort 1 048 subjects(38.5 %). These subjects were followed up for 1-19 years, averaged 10.88 years. The outcome of death from stomach cancer in the exposure cohort was 33, and in the non-exposure cohort 11. After adjustment for age and sex, RR=1.9850 (P=0.0491), 95 % CI was 1.0026, and 3.9301. The results of conditional logistic regression showed an OR of 4.467 and 95 % CI of 1.161, and 17.190 for the nested case control study. CONCLUSION: The results from the retrospective cohort study and the nested-case control study on the association of H. pylori infection and gastric cancer in China suggested that Helicobacter pylori infection might increase the risk of stomach cancer.     

Helicobacter pylori infection and markers of gastric cancer risk in Alaska Native persons: A retrospective case-control study

BACKGROUND:

Alaska Native persons experience gastric cancer incidence and mortality rates that are three to four times higher than in the general United States population.

OBJECTIVE:

To evaluate pepsinogen I, pepsinogen I/II ratio, anti-Helicobacter pylori and cytotoxin-associated gene A (CagA) antibody levels, and blood group for their associations with gastric cancer development in Alaska Native people.

METHODS:

The present analysis was a retrospective case-control study that matched gastric cancers reported to the Alaska Native Tumor Registry from 1969 to 2008 to three controls on known demographic risk factors for H pylori infection, using sera from the Alaska Area Specimen Bank. Conditional logistic regression evaluated associations between serum markers and gastric cancer.

RESULTS:

A total of 122 gastric cancer cases were included, with sera predating cancer diagnosis (mean = 13 years) and 346 matched controls. One hundred twelve cases (91.8%) and 285 controls (82.4%) had evidence of previous or ongoing H pylori infection as measured by anti-H pylori antibody levels. Gastric cancer cases had a 2.63-fold increased odds of having positive anti-H pylori antibodies compared with their matched controls (P=0.01). In a multivariate model, non-cardia gastric cancer (n=94) was associated with anti-H pylori antibodies (adjusted OR 3.92; P=0.004) and low pepsinogen I level (adjusted OR 6.04; P=0.04). No association between gastric cancer and blood group, anti-CagA antibodies or pepsinogen I/II ratio was found.

CONCLUSION:

Alaska Native people with gastric cancer had increased odds of previous H pylori infection. Low pepsinogen I level may function as a precancer marker for noncardia cancer.     

Helicobacter pylori infection and gastric cancer

Gastric cancer remains a major health burden on many societies claiming hundreds of thousands of lives every year. The discovery of Helicobacter pylori has no doubt revolutionised our understanding of this malignancy, which is now regarded as a paradigm for infection-induced chronic inflammation-mediated cancer. In this paper, we discuss the evidence for the association between H. pylori and gastric adenocarcinoma and MALT lymphoma. We also discuss the pathogenesis of these two forms of cancer and the factors that determine their outcome. There is no doubt that the knowledge accumulated over the past two decades will be translated into eventual victory over this killer cancer, largely because we now appreciate that the best way to prevent the cancer is by preventing acquisition of the infection in the first place, or by eradicating the infection in infected subjects. Defining the optimal timing of intervention is going to be the challenge facing us over the next two decades.     

Helicobacter pylori infection and gastric cancer

According to several prospective controlled epidemiologic studies, the positive rate of H. pylori antibody was shown to be higher in the patients with gastric cancer than in the control group. Retrospective studies on the association between gastric cancer and H. pylori have been conducted in a large number of subjects and the results can be classified broadly into two categories, i.e., findings affirming an association and others denying it. Research concerning the association between gastric cancer and H. pylori has achieved great progress over time, leading to the recognition of this relationship by the WHO. One of the greatest concerns is to ascertain whether the final outcome of H. pylori-induced gastritis may lead to gastric cancer. The onset of gastric cancer can be explained as being caused not only by H. pylori infection, but also by a combination of various factors such as food and the environment. However, the possibility that the occurrence of gastric cancer, like the recurrence of peptic ulcer, can be prevented by eradication of H. pylori has also been suggested. Further progress in clinical research is needed to resolve this issue.     

Helicobacter pylori infection and early gastric cancer

BACKGROUND: Helicobacter pylori has recently been associated with an increased risk of gastric cancer. This study aimed to examine the association between H. pylori, histologic chronic gastritis, and intestinal metaplasia in early gastric cancers of different histologic types. STUDY: Seventy-four patients who were surgically diagnosed as having early gastric cancer were included in this study. All tissue specimens were obtained from patients by endoscopic biopsy and were classified histopathologically as intestinal-type early gastric cancer in 55 patients and diffuse-type early gastric cancer in 19 patients. RESULTS: H. pylori infection was found in 67 patients (90.5%) but not found in seven (9.5%). And the prevalence of H. pylori infection with nongastric cancer patients was also high (68.5%). There was no significant difference between the intestinal-type and the diffuse-type early gastric cancer in chronic active gastritis and atrophic chronic gastritis. Intestinal metaplasia was observed more frequently in patients with the intestinal-type than with the diffuse-type early gastric cancer (P = 0.0102). CONCLUSIONS: Infection with H. pylori has an important relationship to both histopathologic types of early gastric cancer.     

Endoscopic Kyoto classification of Helicobacter pylori infection and gastric cancer risk diagnosis

Recent advances in endoscopic technology allow detailed observation of the gastric mucosa.Today,endoscopy is used in the diagnosis of gastritis to determine the presence/absence of Helicobacter pylori(H.pylori)infection and evaluate gastric cancer risk.In 2013,the Japan Gastroenterological Endoscopy Society advocated the Kyoto classification,a new grading system for endoscopic gastritis.The Kyoto classification organized endoscopic findings related to H.pylori infection.The Kyoto classification score is the sum of scores for five endoscopic findings(atrophy,intestinal metaplasia,enlarged folds,nodularity,and diffuse redness with or without regular arrangement of collecting venules)and ranges from 0 to 8.Atrophy,intestinal metaplasia,enlarged folds,and nodularity contribute to gastric cancer risk.Diffuse redness and regular arrangement of collecting venules are related to H.pylori infection status.In subjects without a history of H.pylori eradication,the infection rates in those with Kyoto scores of 0,1,and≥2 were 1.5%,45%,and 82%,respectively.A Kyoto classification score of 0 indicates no H.pylori infection.A Kyoto classification score of 2 or more indicates H.pylori infection.Kyoto classification scores of patients with and without gastric cancer were 4.8 and 3.8,respectively.A Kyoto classification score of 4 or more might indicate gastric cancer risk.     

Helicobacter pylori infection and the risk of gastric malignancy

OBJECTIVE: This prospective cohort study investigated the impact of Helicobacter pylori infection on the development of various gastric malignancies. METHODS: We prospectively followed up 1,225 dyspeptic Taiwanese who had nonulcer dyspepsia, gastric ulcers, or duodenal ulcers at enrollment. Among them, 618 (50.4%) had H. pylori infection and 607 (49.6%) did not. Patients underwent endoscopy at enrollment and at 1- to 3-yr intervals thereafter. RESULTS: During a mean follow-up of 6.3 yr, gastric adenocarcinoma developed in 7 of the 618 H. pylori-infected patients, but in none of the 607 uninfected patients (1.1%vs 0.0%, P= 0.015). The incidence of gastric lymphoma was 0.2% (1/618) and 0% in H. pylori-infected and uninfected patients. Taken together, the development rate of gastric malignancy in H. pylori-infected patients was significantly higher than that in uninfected patients (1.3%vs 0%, P= 0.007). Among H. pylori-infected subjects, the incidence of gastric malignancy was similar between those receiving and not receiving eradication therapy (1.4%vs 1.2%). Multivariate analysis showed that intestinal metaplasia was the only independent factor predicting subsequent development of gastric malignancy in H. pylori-infected subjects with an odds ratio of 4.5 (95% CI 1.1-19.1). CONCLUSIONS: In this prospective cohort study, all gastric malignancies, including adenocarcinoma and lymphoma, developed in H. pylori-infected patients. The finding implies that H. pylori is a necessary cause of most gastric malignancies. Follow-up for H. pylori-infected patients who have intestinal metaplasia is indicated.     

Histological analysis of gastritis and Helicobacter pylori infection in patients with early gastric cancer: a case-control study

BACKGROUND AND AIMS: Infection with Helicobacter pylori is associated with an increased risk of gastric adenocarcinoma. However, most patients with H. pylori infection will not develop gastric cancer. The aims of the present study were to examine which histological features, including H. pylori infection, would increase the risk of gastric cancer using a case-control study. METHODS: Three gastric biopsy specimens were taken from 72 patients with early gastric cancer and 72 age- and sex-matched control subjects. The grade of gastritis was examined according to the updated Sydney System. The presence of H. pylori infection was determined by serology and histology. Odds ratio (OR) of developing gastric cancer was calculated for H. pylori positivity and histological features using conditional logistic regression. For patients with H. pylori infection, histological features in cancer patients and control subjects were compared. RESULTS: The OR of the presence of mononuclear cell infiltration in the corpus and intestinal metaplasia in the angulus were significantly elevated. The grade of mononuclear cell infiltration in the corpus and antrum was significantly higher in both types of cancer patients than controls. Glandular atrophy and intestinal metaplasia were increased in patients with intestinal-type cancer in the angulus and antrum. Bacterial density in the corpus and polymorphonuclear cell infiltration in the antrum were increased in patients with diffuse-type cancer. CONCLUSIONS: Severe chronic gastritis induced by H. pylori infection seems to be associated with diffuse-type gastric cancer. Glandular atrophy and intestinal metaplasia, which occur in gastric mucosa with chronic inflammation, are significantly associated with intestinal-type cancer.     

Helicobacter pylori infection and gastric cancer in Spain

Helicobacter pylori infection has a pathogenic role in the biologic process of gastric carcinoma and gastric MALT lymphoma. Geographical variations in both H. pylori infection and gastric carcinoma prevalence have been reported. The outcome of H. pylori chronic gastritis varies among individuals depending, in part, on the environmental factors. Atrophic gastritis and intestinal metaplasia are risk factors of gastric carcinoma. The prevalence of gastric carcinoma in Spain differs from being high in the central areas and low around the Mediterranean coast. The different geographical distribution supports the hypothesis of the intervention of the environmental carcinogenic factors (food, H. pylori, soil chemical compounds etc.). The overall seroprevalence of H. pylori infection is higher in gastric carcinoma patients than in healthy control subjects of the same age. The seroprevalence of H. pylori is higher in Spaniards with the intestinal type of gastric carcinoma than in those with the diffuse type.     

Helicobacter pylori infection and the risk of gastric cancer among the Korean population

Helicobacter pylori infection has been associated with chronic atrophic gastritis, a precursor of gastric cancer. We conducted a prospective, case-controlled study to investigate whether H. pylori infection increases the risk of gastric cancer in Korean people with a high risk of gastric cancer. We enrolled 160 gastric cancer patients who were confirmed by endoscopic biopsy during 1994 and 160 age-matched control subjects with non-ulcer dyspepsia were compared to document the relationship between H. pylori infection and gastric cancer. The presence of H. pylori infection was determined by the rapid urease test and/or histology by Wright-Giemsa staining. The overall presence of H. pylori infection was 60% in gastric cancer patients and 51.9% in age-matched control subjects (odds ratio 1.39; 95% confidence interval 0.894–2.17; P= 0.143). Carcinomas of cardia, body and antrum were not associated with H. pylori infection (odds ratio 1.43, 1.69 and 1.29, respectively; 95% confidence interval, 0.271–7.52, 0.787–3.62 and 0.689–2.43, respectively; P= 0.178, 0.177 and 0.642, respectively) nor was the intestinal or diffuse type of cancer (odds ratio 1.39 and 1.40, respectively; 95% confidence interval 0.791–2.45 and 0.681–2.87, respectively; P= 0.250 and 0.835, respectively). Gender was not a risk for gastric cancer. In contrast to previous studies, these results do not provide evidence of H. pylori infection for gastric carcinogenesis in Korea.     

Inducible nitric oxide synthetase genotype and Helicobacter pylori infection affect gastric cancer risk

AIM:To investigate the association of the inducible nitric oxide synthetase(iNOS) C150T polymorphism with Helicobacter pylori(H.pylori) infection and gastric cancer(GC) risk in Iran.METHODS:In order to determine whether there was a correlation between iNOS genotype and GC in Iran,we conducted a case-control study using samples from 329 individuals.For each sample,the C150T iNOS polymorphism was genotyped by polymerase chain reaction(PCR) and restriction digestion.Patients were grouped by cancer presence,demographic and behavior characteristics,and H.pylori infection status.Statistical tests were conducted to determine whether any behavioral factors or a particular iNOS genotype was associated with GC in the study population.RESULTS:In this population,we found that smoking,hot beverage consumption,a familial history of GC and H.pylori infection status were significantly associated with GC development(P = 0.015,P 0.001,P = 0.0034,and P 0.015,respectively).The distribution of the C150T iNOS genotypes among the two study groups was not statistically significant alone,but was impacted by H.pylori infection status.When compared to the non-H.pylori infected group,cancer patients who had a heterozygous CT genotype and were also infected with H.pylori were 2.1 times more at risk of developing GC [odds ratio(OR) = 2.1,P = 0.03] while those with a homozygous TT genotype and infected with H.pylori were 5.0 times more at risk of developing GC(OR = 5.0,P = 0.029).In contrast,this association was not seen in patients in the control group.CONCLUSION:A CT or TT polymorphism at position 150 in the iNOS gene significantly increases the risk of GC and may be a marker for GC susceptibility.     

Helicobacter pylori infection,host genetics and gastric cancer

Helicobacter pylori infects half the world's population and is responsible for a considerable global health burden, including peptic ulcer disease and gastric cancer. The infection causes a chronic gastritis, the severity and distribution of which determine the clinical outcome. Bacterial, environmental and host genetic factors combine to define the degree of gastric damage. Most patients have a limited mild pan‐gastritis with no significant clinical consequences. Antral‐predominant gastritis is associated with high gastric acid output and an increased risk of duodenal ulcers. Corpus‐predominant gastritis is associated with a reduction in gastric acid, multifocal gastric atrophy and an increased risk of gastric cancer. Host genetic factors are particularly important in defining the severity and extent of Helicobacter‐induced gastritis. The most relevant and consistent genetic factors uncovered thus far are in the interleukin‐1 and tumor necrosis factor‐A gene clusters. These cytokines appear to play a key role in the pathophysiology of gastric cancer and their roles have been confirmed in animal models that mimic human gastric neoplasia. More genetic factors have also been uncovered and, with advancing technology, there is every prospect of defining a full genetic risk profile in the next decade. This will aid in targeting the testing and treatment of Helicobacter pylori, which offers a true opportunity to prevent and defeat this global killer.     

Intestinal metaplasia of gastric cardia and carditis in Japanese patients with Helicobacter pylori infection

AIM: The purpose of this study was to determine the prevalence of intestinal metaplasia of the gastric cardia in Japanese patients with Helicobacter pylori infection. METHODS: One hundred and fifty-seven patients with H. pylori infection participated in this study. Four biopsy specimens were taken from antrum, lesser and greater curvatures of stomach, and cardia for histological examination. The patients were divided into three groups: those < or = 39 years of age (group A), those 40-59 years old (group B), and those > or = 60 years of age (group C). RESULTS: The proportions of the patients with intestinal metaplasia of the gastric cardia in the three groups were 12, 39, and 65%, respectively. Their intestinal metaplasia of gastric cardia scores were 0.2, 0.54, and 0.81, respectively (significant difference among groups A, B, and C: p < 0.05), according to the updated Sydney classification. CONCLUSION: The prevalence of intestinal metaplasia of the gastric cardia and carditis in Japanese patients with H. pylori infection was similar to that of metaplasia of antrum and lesser curvature of the stomach.     

Helicobacter pylori and early gastric cancer.

The relation between Helicobacter pylori, intestinal metaplasia, and early gastric cancer was studied by examining gastrectomy specimens from 31 intestinal type and 22 diffuse type carcinomas. A total of 298 patients with antral gastritis were used as controls. Atrophic changes and intestinal metaplasia were significantly more common in intestinal type early gastric cancer compared with diffuse type early gastric cancer (p < 0.05 and p < 0.001, respectively). H pylori was found in 61.3% of intestinal type early gastric cancer and in 54.5% of diffuse type early gastric cancer (NS). The age adjusted prevalence of intestinal metaplasia in the patients with antral gastritis was higher in H pylori positive patients in all age groups studied. Comparing gastritis patients with patients with intestinal type early gastric cancer showed the age adjusted prevalence of intestinal metaplasia to be significantly higher in the patients with early gastric cancer in all age groups studied. In conclusion, H pylori is associated with both types of early gastric carcinoma. Intestinal metaplasia formation seems to be a multifactorial process in which H pylori may play a part. These findings suggest that gastric cancer may be included in the spectrum of H pylori associated diseases, although many questions about causality remain to be answered.