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Abstract

  1. Top of page
  2. Abstract
  3. EPIDEMIOLOGICAL EVIDENCE
  4. HOST GENETIC FACTORS AND GENETIC SUSCEPTIBILITY TO GC
  5. EXPERIMENTAL EVIDENCE
  6. POPULATION-BASED SCREENING
  7. CURRENT RECOMMENDATIONS AND OUTLOOK
  8. REFERENCES

Gastric cancer in the absence of strategies implemented for early detection continues to have a dismal prognosis. There are limited options for a curative therapy once patients present with clinical manifestations of this malignant disease. Helicobacter pylori (H. pylori) infection plays a key role in gastric carcinogenesis, supported by epidemiological, preclinical and clinical studies. The recognition of H. pylori infection as a critical risk factor in the development of gastric cancer opens the chance for new venues in prevention strategies.

Gastric cancer (GC) continues to be a major global health problem. In spite of an impressive fall in its incidence GC still ranks fourth among all cancers and second for mortality, with around 700 000 deaths per year.1,2 The high mortality of patients with GC is due to the fact that clinical manifestations usually become apparent only in an advanced stage, when the effect of current available therapies is very limited.3–5 Few countries in the world like Japan have effective screening strategies that allow the detection of a high number of patients with early GC. Only the detection of early GC offers the chance of adopting curative therapies either by gastric resection or endoscopic mucosal dissection.6–8

The recognition of Helicobacter pylori as critical factor in GC development offers a unique chance to explore new strategies for prevention. The causal role of H. pylori in gastric carcinogenesis is based on epidemiological observations, experimental models, biological plausibility and, most importantly, on clinical observations and therapeutic trials.9,10

EPIDEMIOLOGICAL EVIDENCE

  1. Top of page
  2. Abstract
  3. EPIDEMIOLOGICAL EVIDENCE
  4. HOST GENETIC FACTORS AND GENETIC SUSCEPTIBILITY TO GC
  5. EXPERIMENTAL EVIDENCE
  6. POPULATION-BASED SCREENING
  7. CURRENT RECOMMENDATIONS AND OUTLOOK
  8. REFERENCES

Early reports have signaled that H. pylori-infected individuals have a twofold increased risk of developing GC. A meta-analysis of 12 studies, published in 2000, indicated an almost threefold increased risk and a further sixfold increased risk if serological samples had been taken from patients at least 10 years before GC had been diagnosed.11 This is due to the fact that H. pylori leaves the stomach when extensive gastric atrophy and intestinal metaplasia (IM) take place and the immunological memory gets lost. Recognition of the prolonged persistence of cytotoxin-associated gene A (CagA) antibodies as compared to other H. pylori targeting antibodies allows a more realistic estimation of GC to be given. Using the CagA antibody determination in the sera of patients with GC as a tool, the risk of H. pylori-infected subjects of developing GC was found to be close to 30-fold higher.12,13

A cautious estimation assigned to H. pylori infection an attributable risk of 71% for the development of GC.13 The risk of distal GC in H. pylori-infected subjects relates to both histological types, the intestinal and diffuse type of gastric cancer.14 While in most studies the risk of H. pylori infection is reported to be related only to the distal location of the GC the more recent, meticulous separation of proximal GC from esophageal adenocarcinomas suggests that the proximal GC is H. pylori-related as well.15

In the multifactorial H. pylori-driven pathogenesis of GC bacterial virulence factors interact with host susceptibility factors. Environmental, and particularly dietary, factors are the third important component in this complex pathogenesis.

Virulence determinants of H. pylori

H. pylori is characterized by a high level of genetic diversity and isolates in an individual can change over time, due to DNA rearrangements, recombination events and endogenous mutations.16,17 This diversity can be important for its adaption to the host stomach and also for the clinical outcome of the infection and makes it difficult to identify bacterial virulence factors responsible for the induction of GC. At the time of writing, among bacterial virulence factors identified, the Cag-pathogenicity island (Cag-PAI), the vacuolating cytotoxin (VacA) and the outer-membrane protein BabA have been identified as playing a crucial role in H. pylori-induced gastric carcinogenesis.18

The Cag pathogenicity Island (Cag-PAI)

H. pylori CagA+ strains are associated with higher grades of inflammation and a significantly increased risk of developing GC.17,19H. pylori CagA+ strains contain a genomic region of 40 Kb known as the Cag-PAI. The Cag-PAI encodes a type IV secretion system (T4SS) for the delivery of CagA into the gastric epithelial cells.20,21 An important role in this process is played by CagL, a T4SS-pilus covering protein that allocates the T4SS to β1-integrin on target gastric epithelial cells.22 After translocation into the host cell, CagA can be phosphorylated at its five amino-acid EPIYA repeat region by host Src kinase and later by Abl kinases. Phosphorylated CagA has been reported to interact with specific phosphotyrosine-binding molecules, such as Src homology 2 (SH2) domains.23 Up to now, the tyrosine phosphatase SHP-2, the tyrosine kinase Csk and the adaptor protein Crk were found to bind CagA in a phosphorylation-dependent manner. The binding to the tyrosine phosphatase Shp-2, for example, leads to an activation of the mitogenic Ras-mitogen-activated protein kinase (MAPK) pathway, involving the Ras-dependent kinases ERK1 and 2.24,25 The activation of the MAPK pathway leads to the dephosphorylation of host cell proteins and morphological changes in the epithelial cell. CagA can also activate the Ras-Erk pathway in a Shp-2 independent manner, which leads to an increase of interleukin (IL)-8 release and nuclear factor (NF)-κB activation.26 For a more detailed elucidation of CagA phosphorylation-dependent host cell effects, we refer to two recent reviews.27,28 Independent of its phosphorylation status, CagA can also elicit host cell responses such as the disruption of the apical junction complex of mucosal cells, the loss of cell polarity and proinflammatory and mitogenic responses.28,29

The cytotoxin VacA and the outer membrane protein BabA

The VacA toxin is an important virulence factor in H. pylori-induced pathogenesis. The toxin can induce multiple cellular activities, including cell vacuolation, membrane channel formation, apoptosis and immunomodulation.30–35 For example, VacA blocks the proliferation of T-cells by inducing cell cycle arrest in the G1/S cell cycle phase (G1 defines the ‘gap I’ or ‘growth phase’ when the cell prepares for DNA replication, whereas the S phase represents the step when the DNA synthesis for replication happens), which could explain the persistence of H. pylori infection.36 The toxin is encoded by all H. pylori strains but there is a high genetic diversity among the vac alleles.34,37 The regions of major diversity are localized to the VacA secretion signal sequence (allele types s1 and s2) and the mid-region (m1 and m2). The s1 and m1 vac allele are the most extensively studied ones, and the presence of those alleles is strongly correlated with the expression of the Cag-PAI.38,39 Strains expressing the combination of these alleles and Cag-PAI show enhanced epithelial cell injury.34,35

Depending on the geographical region, 40∼95% of H. pylori strains express the outer membrane protein BabA.40 The expression of BabA enables H. pylori to effect maximal adherence to the gastric epithelium. BabA binds the Lewis b blood antigen and other related ABO antigens to the epithelial cells of the gastric mucosa.41 Patients infected with a BabA positive strain show a higher density of bacterial colonization in the stomach and have an enhanced inflammation due to increased IL-8 levels.42 Interestingly, the presence of BabA is associated with the presence of the s1 allele of VacA and CagA and it is known that the H. pylori strains expressing all three genes are associated with the highest risk for developing GC.43

HOST GENETIC FACTORS AND GENETIC SUSCEPTIBILITY TO GC

  1. Top of page
  2. Abstract
  3. EPIDEMIOLOGICAL EVIDENCE
  4. HOST GENETIC FACTORS AND GENETIC SUSCEPTIBILITY TO GC
  5. EXPERIMENTAL EVIDENCE
  6. POPULATION-BASED SCREENING
  7. CURRENT RECOMMENDATIONS AND OUTLOOK
  8. REFERENCES

In recent years, more and more evidence has been gathered that host genetic factors have a significant impact in the clinical outcome and anatomical distribution of H. pylori infection. Polymorphisms in several genes are considered to increase the risk for the development of GC.

Patients carrying the proinflammatory polymorphism of the interleukin-1-beta (IL-1β) and IL-1 receptor antagonist genes have a twofold to threefold increased risk of developing GC compared with patients who have genotypes with less proinflammatory activity.44 Il-1β is a potent proinflammatory cytokine released during H. pylori infection and in addition, is the most powerful acid inhibitor. These results were confirmed in the European Prospective Investigation into Cancer and Nutrition (EPIC) 2008 study, showing that those polymorphisms are associated with an increased risk of non-cardia adenocarcinoma in H. pylori-infected individuals.45

Another proinflammatory cytokine is tumor necrosis factor (TNF)-α, which is also produced in the gastric mucosa in response to H. pylori infection.46 Polymorphisms in this gene are associated with an increased risk of GC.47 A recent study focused on the association between single-nucleotide polymorphisms of the IL-16 gene and GC. IL-16 promotes the secretion of tumor-associated inflammatory cytokines by monocytes. In this study, the authors demonstrated that IL-16 polymorphisms are significantly associated with susceptibility to GC.48 Interferon (IFN) gamma is a key player of the Th1-related cytokines that promote gastritis of patients homozygous for the IFNGR1–56*T allele, who have a fourfold risk of developing early-onset GC compared to heterozygous individuals.49

In addition to the polymorphisms of inflammation-related genes, functional polymorphisms of receptors of the innate immune response, such as toll-like receptors have been reported with an up to 11-fold increased risk for GC.50

H. pylori, environmental factors and GC

For decades the relevance of diet for the development of GC has been under investigation. By 1982 the World Health Organization stated that eating habits are main factors involved in gastric carcinogenesis. This statement was made prior to the discovery of H. pylori by Warren and Marshall in 1983.

Substantial evidence from case-control, epidemiological and cohort studies has been gained over the years demonstrating that a diet high in fruit and vegetables reduces the risk for GC development whereas a high intake of various traditional salt-preserved foods increases this risk. However, prospective studies have so far failed to prove that fruit and vegetables have a protective effect. Thus, the International Agency for Research on Cancer determined that higher intake of vegetables possibly, and higher intake of fruit probably reduce the risk of GC.51 But there is substantial evidence that a high intake of salt-preserved foods and salt per se increases the risk of GC and should therefore be avoided or at least reduced.52

Several potential mechanisms have to be considered through which a diet high in fruit and vegetables may be preventive and protective against GC. Fruit and vegetables are rich in carotenoids, vitamin C, folates and phytochemicals, and have a high anti-oxidant capacity, each of which on its own or in concert may protect against GC. In a recent Cochrane analysis of randomized trials, anti-oxidant supplements were compared with a placebo for the prevention of cancers of the gastrointestinal tract. There was no definite evidence for a preventive effect against GC by anti-oxidants.53

The effects of vitamin C as a protective supplement against GC are also under debate. The reason for this is the complex relationship of vitamin C to H. pylori infection. H. pylori infection reduces the bioavailability of this vitamin, leading subsequently to decreased vitamin C concentrations in the plasma and the gastric juice,54,55 whereas the luminal concentration of reactive oxygen species is increased in association with H. pylori infection.56 The EPIC study analyzed the association of plasma vitamin C with the risk of GC, while taking into account factors like body mass index, total energy intake, smoking and H. pylori status. This study could not demonstrate an association between vitamin C levels and GC development.57 However, a large follow-up study with 3433 participants carried out in a high risk area for GC in China showed that low levels of dietary vitamin C and H. pylori infection may contribute to the progression of precancerous lesions to GC.58

Several studies have reported that smoking itself is an important risk factor for GC development.59,60 About 60 different components in cigarette smoke are considered to be carcinogenic. A recent systematic review analyzed the relationship between cigarette smoking and GC. In this review 42 cohort, case-cohort, and case-control studies were included. The study provided evidence that smoking was significantly associated with an increased relative risk (RR) for both gastric cardia (RR = 1.87; 95% CI: 1.31–2.67) and non-cardia cancers (RR = 1.60; 95% CI: 1.41–1.80).61 This conforms to the results of a large EPIC study that estimated 17.6% (95% CI= 10.5–29.5%) of GC to be related to smoking.62H. pylori infection is usually acquired during early childhood and a smoking career usually starts in adolescence. Thus, the influence of both risk factors starts in early life. An interesting study by Brenner et al. addressed the question whether H. pylori-infected smokers have an increased risk of GC. This study clearly demonstrated that smoking patients with CagA-positive H. pylori infection have a strongly increased risk of GC.63 In conclusion, smoking seems to be the most important behavioural risk factor for GC and the risk increases dramatically in conjunction with H. pylori infection.

EXPERIMENTAL EVIDENCE

  1. Top of page
  2. Abstract
  3. EPIDEMIOLOGICAL EVIDENCE
  4. HOST GENETIC FACTORS AND GENETIC SUSCEPTIBILITY TO GC
  5. EXPERIMENTAL EVIDENCE
  6. POPULATION-BASED SCREENING
  7. CURRENT RECOMMENDATIONS AND OUTLOOK
  8. REFERENCES

Animal experiments

A number of models have been developed to examine gastric carcinogenesis in animals; the most widely used being ferrets, mice and Mongolian gerbils.64–66 In these studies H. pylori was shown to be a weak carcinogen on its own, but in the presence of nitrosamine it leads to a high rate of cancer 1 year following the infection.67–70 The most recent finding in primates (monkeys) lends support to the co-carcinogenetic effect of H. pylori infection with nitrosamines, which are found in pickled vegetables.71

Cell biology

The mechanisms underlying the histological cascade from mucosal inflammation via atrophy, IM and dysplasia to GC and to intestinal type GC, originally described by Correa,72 have recently been unravelled to a great extent (Fig. 1). A direct mutagenic action of H. pylori accompanying the inflammation is more likely to account for the development of diffuse type GC.73H. pylori directly affects gastric epithelial cell signaling, thereby triggering hyper-proliferative processes.28 The bacterium interferes with the activity of growth factor receptors, that is, the epidermal growth factor receptor (EGFR),74 the EGFR-related receptor (Her2/Neu), and the c-Met receptor,75 thus promoting epithelial cell growth and cell survival as well as cell dissociation and cell motility. The best characterized bacterial mechanism leading to H. pylori dysregulation of gastric epithelial cells functions is the type IV secretion system.28 This system translocates the H. pylori oncoprotein, CagA, into the cells.

image

Figure 1. Correa's sequence of gastric cancer (GC) development. Illustrated is the suggested sequence of mucosal alterations induced by Helicobacter pylori infection that will finally lead to the development of GC. The point of no return, when this sequence can no longer be stopped, has not yet been defined.

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Phosphorylated CagA activates a variety of signal systems, among which it promotes cell motility through c-Met receptor activation,75 interacting directly with the adaptor protein Grb2,76 the tyrosine phosphatase SHP-2,23 and phospholipase C.75 Thus, CagA directly interacts with signal transducting proteins and may play a role as an adaptor protein in H. pylori-induced EGFR signalling. To evade apoptosis H. pylori activates receptor inline image (PPARinline image),77 which involves H. pylori-induced cyclo-oxygenase-2 activity.78 Wnt-signalling is also directly activated by H. pylori, leading to β-catenin accumulation and subsequent cell cycle disruption.79–81 The accumulation of β-catenin is detected in 30 percent of patients with GC.82

The complex and evolving pathways of altering cell signals in gastric epithelial cells shed important light on gastric carcinogenesis. The question whether the carcinogenetic process initiates by hitting the gastric stem cells or whether the local tissue destruction and atrophy will attract bone marrow-derived cells for malignant cell cloning in the stomach72 continues to stimulate research and debates.

H. pylori eradication in primary and secondary prevention of GC

H. pylori eradication has the potential to prevent GC and this has been well documented.83 The limitation, however, is that once pre-neoplastic changes (gastric atrophy and IM) have occurred, the prevention of further progression by H. pylori eradication to invasive cancer is less likely.84 Wong et al.were the first to indicate that H. pylori eradication is no guarantee for preventing GC in patients with chronic gastritis and existing pre-neoplastic changes. The critical aspect of best timing for H. pylori eradication has recently been reopened by a study from Japan on 4133 patients with peptic ulcer disease (PUD). Among these patients with PUD and a mean age of 52.9 years the incidence of GC was 1.24% for those receiving H. pylori eradication therapy and 2.56% for those who did not during a 5.6-year follow up.85 There is obviously a point of no return when curing the H. pylori infection no longer permits an effective prevention of GC. The assumption that severe atrophy and IM marks the critical point at which even successful H. pylori eradication may not effectively prevent a malignant process is based on weak grounds; such a progression to cancer occurs only in a subset of these patients. Watari et al. examined the role of H. pylori eradication on the cellular phenotypic characterization of IM. They found that H. pylori eradication can change the phenotype of IM in the stomach although a regression of the histological IM score cannot be observed. The suggestion from this study was that eradication of H. pylori may lead to a reduction in the incidence of GC by a mechanism acting on the cellular phenotype of IM.86 This line of research is certainly worth being pursued further. The characterization of the cellular phenotype of IM should be further explored with the intention to find predictors to arrest the progression of the malignant inflammatory cascade. The consideration of a phenotypical characterization of IM is particularly interesting in the context of recent observations by Fukase et al., who demonstrated that even after an endoscopic resection of early GC, recurrence of metachronous GC is significantly reduced by H. pylori eradication.87

In a multicenter, open-label randomized trial 544 patients following endoscopic resection (EMR) of early gastric cancer (EGC) received either eradication treatment against H. pylori or a placebo regimen. At the 3-year follow up, metachronous GC developed in nine of 272 patients who received eradication treatment (3.3%) and in 24 of the 272 placebo patients (8.8%), resulting in an odds ratio of 0.353 (95% CI 0.161–0.775, P= 0.009). In the modified intention-to-treat analysis adjusted for loss to follow up and respecting the patient population that had received at least one post-treatment assessment of tumor status, a hazard ratio (HR) for metachronous GC of 0.339 was documented (95% CI 0.157–0.729; P= 0.003). From these findings the eradication of H. pylori can be expected to be effective in the secondary prevention of metachronous GC after the endoscopic treatment of EGC, routinely applied. Previous observations along the same lines88,89 have encouraged clinicians to consider H. pylori eradication in patients in whom GC has been removed.

A beneficial side effect of the post-interventional eradication of H. pylori was recently demonstrated by Cheon et al. Of 47 patients who had undergone EMR for EGC, at 4 weeks’ post-treatment there was a significant difference concerning healing of the EMR-induced ulcers in the group with successful H. pylori eradication compared with those receiving proton pump inhibitor therapy alone or those who were not cured with the H. pylori therapy.90

Precancerous lesions: arrest or progression

The role of risk gastritis has been confirmed to carry an increased risk for GC development.91,92 Corpus predominant gastritis, gastric atrophy and IM are the features of risk gastritis. For IM the debate is whether it has a premalignant or a para-malignant role. The increased risk for gastric carcinogenesis of patients with glandular atrophy, IM and dysplastic changes, however, is undisputed.93

The clinical relevance has recently been reinforced in a large retrospective analysis conducted by de Vries et al. The authors evaluated data of 92 250 patients whose records were filed in the Dutch Nationwide Histopathology Registry for the period from 1991 until 2004, and the follow up of registered patients until 2005. Among these patients 22 365 (24%) were diagnosed with atrophic gastritis, 61 707 (67%) with IM, 7616 (8%) with mild or moderate dysplasia and 562 (0.6%) with severe dysplasia. Endoscopic and histopathological follow ups were performed in 26% of patients with atrophic gastritis, 28% with IM and 38% with mild or moderate dysplasia, compared to 61% with severe dysplasia (P < 0.001) and revealed an annual incidence of GC in 0.1% of patients with atrophic gastritis, 0.25% with IM, 0.6% with mild or moderate dysplasia and 6% with severe dysplasia. The resulting HR for severe dysplasia was 40.14 (95% CI 32.2–50.1). Further independent risk factors in multivariate analysis were male gender (HR 1.5; 95% CI 1.3–1.7) and age (HR for 75–84 years 3.75; 95% CI 2.8–5.1).94

The cancer risk in patients with mild or moderate dysplasia was comparable to the risk for the development of colorectal cancer after the removal of colonic adenomas. However, no recommendation for surveillance has been instituted. So far, the best estimate for the regression in histopathology scores can be calculated as a function of the square of the time the patient has been H. pylori negative after eradication therapy.95 The need for guidelines to determine at what intervals patients will require endoscopic control is needed.

POPULATION-BASED SCREENING

  1. Top of page
  2. Abstract
  3. EPIDEMIOLOGICAL EVIDENCE
  4. HOST GENETIC FACTORS AND GENETIC SUSCEPTIBILITY TO GC
  5. EXPERIMENTAL EVIDENCE
  6. POPULATION-BASED SCREENING
  7. CURRENT RECOMMENDATIONS AND OUTLOOK
  8. REFERENCES

As of today general population mass screening for GC is only conducted in high incidence regions in Asia.96

In a large population-based cohort study from Japan with more than 42 000 patients with a 13-year follow up there was no difference in the overall incidence of GC between the screened (endoscopy and photofluorography) and the unscreened group, but a decrease was reported in the incidence of advanced stage GC (RR 0.75; 95% CI 0.58–0.96) and a twofold reduction of GC mortality in the screened versus the unscreened patients (RR 0.52; 95% CI 0.36–0.74).97

Recent retrospective cohort studies from different regions in Asia including between 11 000 and 18 000 patients confirmed these data and revealed a significantly higher proportion of early GC accessible for endoscopic treatment in the group of patients that underwent regular and repeated screening endoscopic examinations.98–100

Endoscopy with sampling of standard biopsies is the best and most reliable option for GC screening. In a Japanese population screening programme about 35 000 patients have been screened each year over a 3-year period. The endoscopy had a sensitivity of 87 percent for GC detection, which was 4.6-fold higher than photofluorography or equivalent radiographic methods. Although the costs per examination were highest for an individual endoscopy, still it was the cheapest means regarding the overall expense required for the management of each individual with GC.101 The cost effectiveness of mass screening for a 24-year period in a study from Singapore estimated the endoscopic screening for stomach cancer to be cost effective in moderate to high-risk populations.102

Apart from population-based screening for the early detection of GC, another option is the primary prevention of GC by screening and treating H. pylori infection. In populations in East Asia with a high incidence of GC compared with regions in Africa, South Asia or Europe, the screen and treat approach is cost effective.103 If expenses for diagnostic and therapeutic procedures in H. pylori infection management are taken into account together in areas with low incidence of GC, this results in the poor cost effectiveness of a ‘screen-and-eradicate’ schedule for the prevention of GC. Parsonnet et al. calculated the costs per life-year saved to be about US$ 25 000, assuming a 30 percent decrease in the incidence of GC by population-based H. pylori screening followed by eradication.104 Several US studies have supported these data, suggesting the costs for H. pylori screening and treatment are between US$ 6300 and US$ 25 000 per life-year saved.105–107 Two UK models confirmed these cost estimates for a screen and treat model.108,109 One model suggesting that H. pylori test-and-treat was cost effective for the public health service further assessed the possible reduction of dyspeptic symptoms and ulcer disease in the community.

In a recent calculation for a high-risk region in China, an empirically calibrated model of GC was used to estimate cost of the reduction of lifetime cancer risk.110 Three options have been considered: (i) a single lifetime screening at the age of 20, 30 or 40; (ii) a single lifetime screening followed by the rescreening of individuals with negative results; and (iii) universal treatment for H. pylori infection at the age of 20, 30 or 40.

Screening and treatment in individuals at the age of 20 resulted in a reduction of the lifetime risk for GC of 14.5% in males and 26.6% in females. The costs did not exceed US$ 1500 per life-year saved. The application of universal treatment even increased the risk reduction by 1.5% and 2.3% for men and women, respectively, but the incremental cost-effectiveness rates exceeded US$ 2500 per life-year saved. Assessing persons at an older age or rescreening negative individuals was not cost effective. Prospective trials on a global scale are needed to further support these theoretical estimations. Unless these results are available, general population-based screening for H. pylori infection with the aim of GC prevention can be recommended only for high incidence regions. Otherwise, searching for H. pylori should be performed in individuals with a risk profile, including patients with peptic ulcer disease (e.g., after curative treatment) and their first-degree relatives111 (Fig. 2).

image

Figure 2. Algorithm for population-based screening and treatment of Helicobacter pylori infection for gastric cancer (GC) prevention.

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CURRENT RECOMMENDATIONS AND OUTLOOK

  1. Top of page
  2. Abstract
  3. EPIDEMIOLOGICAL EVIDENCE
  4. HOST GENETIC FACTORS AND GENETIC SUSCEPTIBILITY TO GC
  5. EXPERIMENTAL EVIDENCE
  6. POPULATION-BASED SCREENING
  7. CURRENT RECOMMENDATIONS AND OUTLOOK
  8. REFERENCES

European and Asian–Pacific Guidelines both have tackled the issue of GC prevention by H. pylori eradication.96,112

The European consensus report concluded that H. pylori eradication has the potential to reduce the risk of GC, indicated individuals at risk and pointed to the need to identify the best timing for eradication, possibly before the development of pre-neoplastic lesions, but saw a global strategy restricted because of shortcomings of current therapies for such widespread use.112 The Asian–Pacific guidelines went a step further and recommended H. pylori screening and eradication in high-risk populations.96 Caution is expressed concerning patients who have already developed precancerous gastric lesions. These patients need to remain under endoscopic-histological surveillance. The global unrestricted adoption of screen-and-treat for GC prevention awaits new treatments. Ultimately a healthy stomach for all would require an effective vaccine.

REFERENCES

  1. Top of page
  2. Abstract
  3. EPIDEMIOLOGICAL EVIDENCE
  4. HOST GENETIC FACTORS AND GENETIC SUSCEPTIBILITY TO GC
  5. EXPERIMENTAL EVIDENCE
  6. POPULATION-BASED SCREENING
  7. CURRENT RECOMMENDATIONS AND OUTLOOK
  8. REFERENCES