Helicobacter pylori screening and gastric cancer.
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Helicobacter Infections↗
Biomedical subjects
D Forman
Publications and source records attributed to D Forman.
An apparent lack of association between Helicobacter pylori infection and risk of gastric cancer in China.
Several prospective studies have shown a significant association between Helicobacter pylori seropositivity and the risk of gastric cancer. Only a small proportion of H. pylori-infected individuals will, however, develop gastric cancer, and it is unclear what effects other factors, such as diet, might have on the risk of cancer. Eighty-seven subjects with gastric cancer were identified during the first 6 years of follow-up (mean 2.4 years) of a cohort of middle-aged men from Shanghai, China. They were matched with 261 cancer-free controls, and serum samples from all subjects, obtained at recruitment, were assayed for anti-H. pylori IgG antibodies. Questionnaire data provided information on a wide range of socio-demographic life-style and dietary variables. H. pylori seropositivity rates in the cases and controls were 54% and 56%, respectively. Neither the overall risk of developing gastric cancer nor the risk of developing non-cardia gastric cancer was significantly associated with prior M. pylori seropositivity. Adjustment for any of the other medical, dietary or life-style variables studied had little effect on the risk of developing non-cardia gastric cancer; simultaneous adjustment for all of these factors yielded an odds ratio of 1.17. The results do not support the hypothesis that H. pylori plays a role in the process of gastric carcinogenesis in China. It is possible that this is an artefact resulting from the relatively short follow-up period to date.
Antibodies, Bacterial↗
Specialist surgeons and survival in breast cancer. Observational studies are essential.
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Breast Neoplasms↗
Helicobacter pylori gastritis and serum pepsinogen levels in a healthy population: development of a biomarker strategy for gastric atrophy in high risk groups.
This study aimed to estimate the prevalence and type of chronic gastritis in an asymptomatic working population and to determine whether a combination of serum pepsinogen levels and Helicobacter pylori serology could be used to identify a subgroup with atrophic gastritis at elevated risk of gastric carcinoma. A 10% subsample of 544 male volunteer factory workers aged 18-63 years and participating in a larger study underwent endoscopy and biopsy. Of these men, 29 were seropositive for Helicobacter pylori; all but three (89.7%) had chronic gastritis. Serum pepsinogen A levels increased with progression from a corpus predominant pattern of gastritis through pangastritis to an antral predominant pattern. Nine subjects had corpus atrophy, which was in most cases accompanied by fasting hypochlorhydria and hypergastrinaemia. A combination of pepsinogen A below 80 ng ml-1 and Helicobaceter pylori seropositivity detected corpus atrophy with sensitivity 88.9% and specificity 92.3%. A second screening stage, using a pepsinogen A/C ratio of below 2.5 as a cut-off, resulted in a reduction in numbers requiring further investigation but with some loss of sensitivity (77.8%). Application of this two-stage screening programme to the original sample of 544 workers would have resulted in 11 (2.2%) men being selected for follow-up, excluding 25 (5.1%) false negatives. Our results suggest that a combination of serum pepsinogen levels and Helicobacter pylori serology could be useful as a biomarker strategy for detection of individuals at increased risk of gastric carcinoma and for non-invasive investigation of the natural history of Helicobacter pylori gastritis.
Adolescent↗
High risk of lymphomas in children of Asian origin: ethnicity or confounding by socioeconomic status?
To examine the role of ethnic origin as a risk factor for paediatric lymphoma, a cancer registry-based analysis was undertaken in Yorkshire, UK. Children of Asian ethnic origin were found to have an odds ratio for lymphomas of 1.60 (CI 0.98-2.62), after adjusting for age and sex. After adjusting also for 'super profile group' as an indicator of socioeconomic status, the estimate became 1.99 (CI 1.08-3.68). Hodgkin's disease and non-Hodgkin's lymphomas were analysed separately with similar results. Super profile group is an area-based measure and may not reflect the individual variation in living standards, especially among the Asian immigrants. Our results indicate that socioeconomic status does not confound the relationship between lymphomas and ethnic origin. However, there is a need for studies of ethnicity that include indicators of individual living standards or socioeconomic status.
Adolescent↗
Is Helicobacter pylori transmitted from cats to humans?
BACKGROUND: Subsequent to the isolation of Helicobacter pylori from domestic cats, it has been suggested that the organism might be transmitted from cats to humans. This hypothesis has already gained considerable media attention. MATERIALS AND METHODS: In a previous study of risk factors for H. pylori infection, 447 factory workers from Stoke on Trent in the UK had provided blood samples for H. pylori serological workup. They had also completed a detailed questionnaire concerning their living conditions, including the possession of any household pets, in childhood. Logistic regression was used to assess the association between cat ownership in childhood and H. pylori seropositivity. RESULTS: After adjustment for potential confounders, it was found that subjects who had owned a pet as a child were slightly more likely to be H. pylori seropositive than subjects who had not. There was, however, no difference between subjects who had owned a cat and those with other pets. CONCLUSIONS: These data do not support the hypothesis that H. pylori infection might be transmitted from cats to humans.
Adolescent↗
Aspirin, non-steroidal anti-inflammatory drugs and protection from colorectal cancer: a review of the epidemiological evidence.
There is substantial experimental, clinical and epidemiological evidence that regular use of non-steroid anti-inflammatory drugs (NSAIDs), particularly aspirin, is associated with a reduced risk of colorectal cancer. The protective effect is thought to arise from inhibition of prostaglandin synthesis, although the precise mechanism remains unclear. Of the epidemiological studies carried out, all but one have found that regular use of NSAIDs reduces the risk of colorectal cancer by 30-50%. The consistency of this finding across studies and the magnitude of the reduced risk tend to support a causal association between NSAID use and reduced risk of colorectal cancer. Further, the protective effect increases with longer duration of use, and persists after controlling for other colorectal cancer risk factors. However, these observational studies are limited by inherent biases, potential confounding with other lifestyle factors, and sparse information on dose and duration of use. Only one randomized controlled trial has been carried out, and no reduction in risk was associated with intake of one aspirin per day, though this may be due to the short follow-up period and the low dose of aspirin taken. Further observational studies and randomized controlled trials are needed to confirm the association, to quantify the dosage required for a protective effect, and to identify those patients most likely to benefit.
Adenoma↗
Helicobacter pylori and gastric cancer.
The International Agency for Research on Cancer, sponsored by the World Health Organization, has recently categorized Helicobacter pylori infection as a class I carcinogen, based on evidence that this infection increases the risk of gastric cancer. The classification was intentionally qualitative in nature and not associated with any public health recommendations. In addition, no specific causal mechanism was proposed to explain the relationship between H. pylori and gastric cancer. In this paper, the magnitude of the risk, implications of the relationship for the prevention of gastric cancer and nature of the causal mechanisms are considered. Relative risk of gastric cancer may be substantial; even with conservative assumptions, the proportion of new cases of gastric cancer worldwide attributable to H. pylori infection is approximately one third of a million annually. This figure is likely to increase with changes in the age structure of the population, and the eradication of H. pylori as a means of prevention of gastric cancer should be considered. A strategy of screening populations in middle age and treating those infected could be relatively inexpensive to administer, but the efficacy is totally unknown and requires evaluation in a randomized controlled trial. Studies designed to address this issue in the general population would need to be large and long-term if gastric cancer is used as an end-point. With respect to carcinogenic mechanisms, a number of constitutive properties of H. pylori may be of relevance to cancer without being specifically carcinogenic. Thus ammonia, which is produced in abundance as a result of urease activity, may promote cell division. Other relevant properties result from the immune response of the host to the bacterium. For example, the excessive production of reactive oxygen metabolites can lead to extensive DNA damage and molecular mutations.
Female↗
Helicobacter pylori and gastric cancer.
Epidemiological studies have consistently shown an association between infection with Helicobacter pylori and gastric cancer. The strongest evidence comes from three prospective studies that have shown the risk of gastric cancer to be increased by about fourfold in infected individuals. This raises the possibility of preventing a substantial number of gastric cancer cases by controlling H. pylori. Screening asymptomatic populations and eradicating the organism in those infected is the only treatment strategy currently available, but several questions remain to be answered before this can be recommended as a routine public health measure. Research into H. pylori has transformed understanding of the aetiology of gastric cancer, focusing attention on factors such as chronic inflammation, impaired host defence mechanisms and oxidative cell damage.
Helicobacter Infections↗
Helicobacter pylori transmission: evidence from a comparison with hepatitis A virus.
OBJECTIVE: To assess the possibility that faecal-oral contact might play a role in the transmission of Helicobacter pylori. DESIGN: A cross-sectional comparison of the patterns of hepatitis A and H. pylori seropositivity. METHODS: At interview, blood samples and questionnaire data were collected from a group of 467 male volunteers, aged 18-65, from Stoke-on-Trent, UK. Serum samples from each subject were then analysed for anti-H. pylori and anti-hepatitis A antibodies. RESULTS: Overall, 100 of 175 H. pylori seropositive subjects (57.1%) and 113 of 292 H. pylori seronegative subjects (38.7%) were hepatitis A seropositive (chi 2 = 15.0, P < 0.001). This difference was not statistically significant after adjustment for age group and father's occupation, as a surrogate for socioeconomic status in childhood (P = 0.15). The seroprevalence of hepatitis A increased with age at a rate of 2.3% per year, compared to only 1.0% per year for H. pylori (P = 0.015). CONCLUSION: These data suggest that the case for faecal-oral transmission of H. pylori, in a manner similar to the spread of hepatitis A, is not proven and that other modes of transmission, for instance through oral-oral contact, should also be considered.
Adult↗
Helicobacter pylori and gastric cancer.
The International Agency of Research on Cancer, sponsored by the World Health Organization, has categorized Helicobacter pylori infection as a class I carcinogen and a definite cause of human gastric cancer. This decision was made largely on the basis of epidemiological evidence relating infection with H. pylori to the aetiology of gastric carcinoma and gastric lymphoma. Epidemiological studies suggest that at least 30% of gastric cancers in the developed world and 50% of those in the developing world may be attributed to H. pylori (although these figures might be as high as 75% and 90% respectively). Prevention of these cancers would result in a considerable saving in terms of morbidity, mortality and health service resources. A strategy of screening populations in middle age and treating those infected could be relatively inexpensive to administer but the efficacy is totally unknown and requires evaluation in a randomized controlled trial. Studies designed to address this issue in the general population would need to be large and long-term if gastric cancer is used as an end-point. With respect to carcinogenic mechanisms, H. pylori affects several aspects of gastric epithelial cell function that may be related to cancer. Notably, cell proliferation is significantly elevated, thus increasing the likelihood of unrepaired genetic lesions and DNA mutations.
Cell Transformation, Neoplastic↗
Trends in incidence of testicular cancer in boys and adolescent men.
Several epidemiological studies have described increasing trends over time in the incidence of testicular cancer in adult men. Less attention has been given to the trends in young boys, adolescents and old men. This paper describes the incidence of testicular cancer in young boys (0-4 years) and adolescents (15-19 years) in Denmark, Norway and Sweden, and compares these trends with the corresponding data on adults. Although only small numbers were available, the data suggest that the incidence of testicular cancer in young boys has been constant, at a level around 0.5 per 100,000. This observation lends support to the idea that testicular cancer in young boys is aetiologically distinct from testicular cancer in adults. In all three populations we found a particularly high average annual increase in the incidence of testicular cancer in adolescents (around 6% per year). It is proposed that this increase is mainly caused by a secular trend towards earlier age at puberty.
Adolescent↗
Helicobacter pylori as a risk factor for cancer.
In 1985, gastric cancer was the second most common cause of cancer death in the world. The rapid decline in gastric cancer rates over the last few decades has been attributed to a decline in the prevalence of environmental risk factors for gastric cancer and/or an increase in the prevalence of protective factors. One such risk factor could be the bacterium Helicobacter pylori. Epidemiological studies have shown that areas with high gastric cancer rates often have a correspondingly high prevalence of H. pylori and prospective studies have shown that subjects with serological evidence of H. pylori infection were significantly more likely to go on to develop gastric cancer than those who did not. Helicobacter pylori itself does not appear to be either genotoxic or mutagenic. Infection is, however, associated with increased cell turnover, a chronic immune response accompanied by increased levels of reactive oxygen metabolites and a reduction in gastric levels of ascorbic acid, all conditions that could favour the development of cancer. Nonetheless, the majority of those who are infected with H. pylori do not go on to develop gastric cancer and other factors, such as the strain of the infecting organism or consumption of dietary antioxidants including vitamin C, could also affect the risk of cancer. Finally, it has been estimated that more than one third, and possibly as many as 90% of gastric cancers might be attributable to infection with H. pylori. Prevention and treatment of infection are, therefore, possible approaches to reducing gastric cancer rates. It is, however, unclear what, if any, effect eradication of the infection would have on an individual's risk of gastric cancer and, to date, anti-Helicobacter therapy has only been shown to be of potential benefit in the treatment of low grade gastric MALT lymphomas.
Chronic Disease↗
Candidate regions for a testicular cancer susceptibility gene.
Epidemiological data suggest the presence of a susceptibility gene for testicular cancer in some families. Families with multiple cases of testicular cancer are rare and almost all those reported have only two affected members. We have performed a sib-pair analysis on 35 families in which there are either two or three affected brothers. These families have been typed for 220 autosomal microsatellite markers spaced 10-20 cM throughout the genome. Six regions which gave a LOD score of more than 1.0 on formal linkage analysis or a P value of 0.05 or less using a non-parametric approach are considered as candidate regions for a susceptibility gene. Of particular interest is one region on chromosome 4. Two neighbouring probes in this region both scored positively with LOD score of 2.60 on multipoint analysis. An International Testis Cancer Linkage Consortium has been formed to pool resources and will investigate these findings further with the world-wide collection of families.
Genetic Linkage↗
Helicobacter pylori and upper gastrointestinal disease: a survey of gastroenterologists in the United Kingdom.
The objective of this study was to conduct a survey of the opinions and practices of gastroenterologists in the United Kingdom concerning the impact of Helicobacter pylori infection on the management of upper gastrointestinal diseases. A postal questionnaire was sent to all medically qualified members of the British Society of Gastroenterology working in the UK. Replies were received from 670 of 1037 eligible BSG members (65%). Of these, 73% thought that H pylori was a cause of duodenal ulcer and 84% thought that eradication of H pylori decreased ulcer recurrence in comparison with acid suppression. While 80% used anti-H pylori therapy for a chronic relapsing duodenal ulcer, only 25% used such therapy for an ulcer at first presentation and 17% never used anti-H pylori therapy for patients with duodenal ulcer. Although 75% of respondents did not agree that H pylori was a cause of non-ulcer dyspepsia, 69% used anti-H pylori therapy to treat a patient with this condition. At the time of the survey, 69% of those who used anti-H pylori therapy adopted some variant of standard triple therapy. Only 7% routinely tested for bacterial sensitivity to antibiotics and only 22% assessed their patients for eradication after treatment. There was a lack of consensus about whether H pylori was a cause of gastric ulcer or gastric cancer with only 47% and 17% respectively believing in these associations. In conclusion, at the time of the survey, the use of anti-H pylori therapy had been accepted by a majority of specialist UK gastroenterologists in the management of upper gastrointestinal disease. There was, however, a substantial degree of uncertainty and divergence about which patients should be treated.
Adult↗
Lead alters growth and reduces angiotensin II receptor density of rat aortic smooth muscle cells.
Environmental lead (Pb2+) contributes a small but significant risk to human hypertension. It is postulated that the hypertensinogenic action of Pb2+ may be due, in part, to its direct action on vascular smooth muscle cells. To investigate this hypothesis, freshly isolated rat aortic smooth muscle (RASM) cells were propagated in defined media containing one of two Centers for Disease Control-based concentrations of Pb2+ (as lead citrate): 100 and 500 micrograms Pb2+/l (i.e., equivalent to 5.5 and 27.5 micrograms Pb2+/dl blood; designated 100-RASM and 500-RASM). Control (CON-RASM) cells received sodium citrate. 500-RASM cells exhibited suppressed propagation and fell out of propagation synchrony with CON-RASM cells: when CON-RASM cell approached confluence (approximately 90%), 500-RASM cell density was 6.4% that of CON-RASM cell density. By contrast, 100-RASM cells exhibited marked hyperplasia albeit this was not apparent until passage 3 (p3). Overall, when p3-p6 CON-RASM cells approached confluence, 100-RASM cell density was 107.6% greater than CON-RASM cell density. The protein content of CON-RASM and 100-RASM was not different, whereas that of 500-RASM cells was 29% greater than that of CON-RASM and 100-RASM cells. Phase-contrast microscopy revealed that 100 micrograms Pb2+/l converted normal spindle-shaped/ribbon-shaped RASM cells into less spread, cobblestone-shaped, neointimal-like cells. Immunocytochemical analysis revealed that 100-RASM cells lacked or had markedly fewer actin cables, characteristic of rapidly dividing cells. In addition, Pb(2+)-treated RASM cells exhibited altered membrane fatty acyl composition with a trend towards an increase (by as much as 50%) in membrane arachidonic acid. Interestingly, hyperplastic 100-RASM cells exhibited a 70.6% reduction in angiotensin II (Ang II) receptor concentration whereas the concentrations of alpha 1- and beta-adrenergic and atrial natriuretic peptide (ANP) receptors were not affected. In addition, in experiments designed to control for Pb(2+)-associated differences in RASM cell propagation, there was a concentration-dependent decrease in Ang II receptor concentration: for 100 and 500 micrograms Pb2+/l, Ang II receptor concentration was decreased 39.6% and 65.5%, respectively. Thus, although Pb2+, depending on its concentration, had contrasting effects on RASM cell propagation, it had a consistent, concentration-dependent inhibitory effect on Ang II receptor concentration. Recovery (r) from Pb2+ required at least two additional passages. At p71r the enhanced propagation (+54%) and reduced Ang II receptor concentration (-49%) of 100r-RASM cells persisted.(ABSTRACT TRUNCATED AT 400 WORDS)
Actins↗
Improved experimental cancer therapy by radioantibody dose intensification as a result of syngeneic bone marrow transplantation.
Myelosuppressive toxicity is dose-limiting for radioimmunotherapy. We have reported on the use of cytokine intervention (rhIL-1 and rmGM-CSF) to stimulate differentiation of progenitor cells and reduce radioantibody-induced leukopenia and thrombocytopenia (J. Natl. Cancer Inst. 84:399, 1992; Cancer 73:1073, 1994). As an alternative to the use of cytokines, we investigated the effect of syngeneic bone marrow transplantation on the ability to dose-escalate radioantibody. Injection of 10(7) bone marrow cells from a donor mouse 6 to 8 days after a 340- to 360-microCi dose of radioantibody (LD100/28)--a 25 to 30% increase above the maximal tolerated dose--resulted in 100% survival. This observation is associated with a recovery in neutrophil and thrombocyte counts within 21 days of therapy (normal recovery after 275 microCi takes 42 days). None of the mice survived when BMT was done at either 4 or 11 days after radioantibody. Marrow from normal donor mice was more effective than that from cytokine-primed mice whose marrow cells were actively cycling after a 5-day course of IL-1/GM-CSF. The combination of the two myeloprotective approaches, BMT plus a 14-day schedule of IL-1 (2 x 10(3) U/d) and GM-CSF (1 microgram/d) intervention, provided a greater stimulation of peripheral WBC counts than either approach alone; however, further dose escalation under these conditions was not feasible. The 30% intensification in radioantibody dose offers a therapeutic advantage for both bulky disease (GW-39 subcutaneous nude mouse model) and micrometastatic disease (GW-39 intrapulmonary model). In the bulky tumor model, the increase in administered dose resulting from BMT extends the 8-week growth delay observed at 275 microCi 131I-MN-14 IgG by an additional 7 weeks. In the metastatic model, dose intensification increased median animal survival from 15 to 23 weeks. Therefore, by optimizing the use of BMT, a greater therapeutic benefit can be derived from radioantibody therapy in a solid tumor model. This study represents a proof of principle, that BMT can be effective for low-dose-rate therapy as it has been for short-duration intense chemotherapy and radiation therapy. It also highlights several important issues to consider when attempting to apply the method in the clinic.
Animals↗
The prevalence of Helicobacter pylori infection in gastric cancer.
The prevalence of Helicobacter pylori infection in gastric cancer patients is difficult to estimate because the infection may be lost from individuals with cancer or its precursor conditions. The bacterium does not colonize cancerous tissue and therefore studies using histopathology as a means of assessing infection require gastric biopsy material sampled separately from the tumour itself. Results from five such studies, with more than 50 patients, have demonstrated an H. pylori prevalence of 43%-78%. Studies using serological assessment of antibody presence have the advantage of enabling adequate case-control comparisons. Ten reported studies that were retrospective in design showed a range in prevalence from 52% to 89% among the cases and from 38% to 78% among the controls. Five studies showed a significant increase in infection prevalence among the cases, with odds ratios ranging from 1.6 to 4.2. The odds ratio increased in subjects who were younger. Retrospective studies may be biased in that the prevalence of H. pylori among cases may be systematically under-estimated. Three prospective serological studies showed a prevalence of 69%-95% among cases and 47%-76% among controls. All three studies had a significantly elevated odds ratio and a pooled estimate of this was 3.8 (95% CI: 2.3-6.2). In the pooled analysis there was a significant trend towards an increased odds ratio with increased time between the assessment of infection and cancer diagnosis. After 14 years of follow-up the overall infection prevalence among cases was 90% and the odds ratio was 8.7 (95% CI: 2.7-45.0). This might represent the best estimate of infection prevalence and associated risk.(ABSTRACT TRUNCATED AT 250 WORDS)
Helicobacter Infections↗