Abstract
Gastric cancer is a major health burden and is the fifth most common malignancy and the third most common cause of death from cancer worldwide. Development of gastric cancer involves several aspects, including host genetics, environmental factors, and Helicobacter pylori infection. There is increasing evidence from epidemiological studies of the association of H. pylori infection and specific virulence factors with gastric cancer. Studies in animal models indicate H. pylori is a primary factor in the development of gastric cancer. One major virulence factor in H. pylori is the cytotoxin-associated gene A (cagA), which encodes the CagA protein in the cag pathogenicity island (cag PAI). Meta-analysis of studies investigating CagA seropositivity irrespective of H. pylori status identified that CagA seropositivity increases the risk of gastric cancer (OR = 2.87, 95% CI: 1.95–4.22) relative to the risk of H. pylori infection alone (OR = 2.31, 95% CI: 1.58–3.39). Eradicating H. pylori is a strategy for reducing gastric cancer incidence. A meta-analysis of six randomised controlled trials (RCTs) suggests that searching for and eradicating H. pylori infection reduces the subsequent incidence of gastric cancer with a pooled relative risk of 0.66 (95% CI: 0.46–0.95). The introduction in regions of high gastric cancer incidence of population-based H. pylori screening and treatment programmes, with a scientifically valid assessment of programme processes, feasibility, effectiveness and possible adverse consequences, would impact the incidence of H. pylori-induced gastric cancer. Given the recent molecular understanding of the oncogenic role of CagA, targeting H. pylori screening and treatment programmes in populations with a high prevalence of H. pylori CagA-positive strains, particularly the more oncogenic East Asian H. pylori CagA strains, may be worth further investigation to optimise the benefits of such strategies.
Highlights
The Global Burden of Gastric CancerGastric cancer is the fifth most common malignancy in the world
In 2009, a new Working Group reviewed considerably more data which had become available since the previous evaluation and reconfirmed that chronic infection with H. pylori is a Group 1 carcinogen with sufficient evidence of causing non-cardia gastric carcinoma and low-grade B-cell gastric MALT lymphoma [7]
The 2009 Working Group noted a substantial increase in the estimated odds ratios (ORs) for the association between H. pylori infection and non-cardia gastric carcinoma in studies using Western blotting assays compared with enzyme-linked immunosorbent assay (ELISA) for the analysis of serum
Summary
Gastric cancer is the fifth most common malignancy in the world (after lung, breast, colorectal and prostate cancers). Mortality rates in Japan and the Republic of Korea are, in comparison with other populations, considerably lower than the corresponding incidence rates This likely reflects the impact of screening and early diagnosis in these countries. Over the 45-year period, incidence rates have steadily declined in most populations with similar trends in both males and females. Despite the global decline in incidence rates over many years, the absolute burden of gastric cancer (number of cases diagnosed) has remained high as a result of population growth and ageing. Whereas most populations show higher rates of non-cardia cancer, this is not consistently the case and in some countries, such as Australia, the USA and the UK, rates are similar to each other [5]
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