Internal Medicine (East Africa); Pathology (East Africa)
Helicobacter pylori is the main cause of peptic ulceration, distal gastric adenocarcinoma, and gastric lymphoma.1 Worldwide, gastric cancer is the second most common malignancy in men and women.1 According to data from the Nairobi Cancer Registry, gastric cancer is the fourth most common malignancy in adult males and the fifth most common in adult females. However, this may not represent the true situation because of under-reporting of cases. In the development of gastric cancer, environmental factors such as smoking, diet and, in particular, infection with H. pylori are significant.1 Based on epidemiological studies, the International Agency for Research on Cancer (IARC) identified H. pylori as a ‘group 1 agent (definite carcinogen)’.2 H. pylori infection can result in decreased acid secretion with subsequent mucosal atrophy and intestinal metaplasia.1 Another precondition for mucosal atrophy is autoimmunity against parietal cells, which can mimic classic autoimmune gastritis with the presence of various autoantibodies in up to 40% of H. pylori-infected individuals.1
The occurrence of intestinal metaplasia, for which a relationship with gastric cancer is strongly suggested, has been demonstrated in approximately 60% of patients with H. pylori infection.1 The metaplasia may then progress to gastric cancer, especially to tumours of the intestinal type.1 Findings by Uemura et al. support the importance of these histological findings as a precancerous condition in H. pyloriassociated gastritis.3 However, only a minority of H. pyloriinfected patients develop gastric cancer, which underscores the notion that the host genetic background could be of critical importance.
Data strongly suggest that the susceptibility to infection from H. pylori is mainly conferred by genes involved in inflammatory processes following colonisation with H. pylori.1 Chronic gastritis is characterised by the release of pro-inflammatory cytokines such as interleukin-1β (IL-1β) or tumour-necrosis factor alpha (TNFα), which are potent inhibitors of gastric acid secretion.1 Advanced-stage gastric cancer has been repeatedly associated with polymorphisms of the IL-1 gene cluster on chromosome 2q, which contains 3 related genes within a 430 kb region (IL-1A, IL-1B, and IL-1RN), encoding for IL-1α , IL-1β, and the endogenous receptor antagonist IL-1ra, respectively. It was hypothesised that genetic differences within these genes could influence the immune response against pathogens such as H. pylori and the development of premalignant histological alterations in the gastric mucosa.1 In patients with advanced-stage gastric cancer, an increased frequency of the IL-1B-31C and IL-1B-511T alleles and the uncommon IL-1B-31C/IL-1B-511T haplotype was demonstrated. In addition, the IL-1RN*2 allele and the homozygous genotype IL-1RN*2/2 were found in increased prevalence in gastric cancers.1 Subsequent studies confirmed these genetic associations.1 El-Omar et al. genotyped patients with gastric cancer according to tumour localisation (cardia v. non-cardia) and oesophageal cancers (adenocarcinomas v. squamous cell carcinomas) for various polymorphisms of genes encoding for pro- and anti-inflammatory cytokines.4 They described an increased risk for non-cardia gastric cancer in carriers of the IL-1B-511T allele, IL-1RN*2 homozygotes, carriers of the TNF-A-308A allele and the haplotype IL-10- 1082A/-819T/-592A. The cumulative risk depends on the number of high-risk alleles or genotypes per patient.4 A previous study confirmed the risk increase for development of gastric carcinoma in carriers of multiple proinflammatory genotypes.1 The alleles IL-1RN*2 and IL-1B-511T are associated with increased synthesis of the proinflammatory cytokine IL-1ß, and the allele TNFA-308A results in an increased production of the proinflammatory cytokine TNF.1
South African Medical Journal
(2009). Prevalence of gastric mucosal interleukin-1 polymorphisms in Kenyan patients with advanced gastric cancer. South African Medical Journal, 99(2), 95-97.
Available at: https://ecommons.aku.edu/eastafrica_fhs_mc_pathol/25
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