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Clinical and environmental risk factors of Helicobacter pylori, gastric cancer, and gastric microbiome signature in a South African cohort

Background: Helicobacter pylori (H. pylori) is a Type 1 carcinogen associated with gastric cancer (GCA) and other gastroduodenal diseases. Despite high H. pylori prevalence in Africa, reported GCA incidence remains paradoxically low, a phenomenon known as the ‘African enigma'. This study aimed to in...

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Main Author: Francis, Innocent Ekparolaguaziba
Other Authors: Setshedi, Mashiko
Format: Thesis
Language:English
English
Published: Department of Medicine 2026
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Summary:Background: Helicobacter pylori (H. pylori) is a Type 1 carcinogen associated with gastric cancer (GCA) and other gastroduodenal diseases. Despite high H. pylori prevalence in Africa, reported GCA incidence remains paradoxically low, a phenomenon known as the ‘African enigma'. This study aimed to investigate the validity of this paradox through a systematic review, retrospective cohort analysis, and prospective study of H. pylori-infected individuals. Methods: The study comprised three components: (1) a systematic review evaluating the epidemiology of GCA in Africa, (2) a retrospective cohort study analyzing GCA incidence and associated risk factors at Groote Schuur Hospital, and (3) a cross-sectional study examining the molecular signature of H. pylori strains and gastric microbiome diversity in affected patients. Results: the systematic review highlighted significant limitations in current data, stressing the need for standardized national registries and comprehensive epidemiological studies. The retrospective study confirmed that GCA mainly affects males aged 60 and above, with non- cardia cancers being the most common subtype. The protective effect of proton pump inhibitors against antral cancer was also observed. The cross-sectional study revealed that the H. pylori strains among Africans had fewer virulence factors (cagPAI variants, virB/D genes) compared to Southeast Asian strains, potentially explaining lower GCA incidence. Additionally, H. pylori infection tends to alter the gastric microbiome diversity, with distinct microbial compositions across racial groups. Conclusions: Findings support the ‘African enigma', suggesting that specific H. pylori strain characteristics and microbiome alterations may contribute to the lower observed GCA incidence in Africa. Future research should integrate multi-omic analyses to further elucidate host-pathogen interactions and disease mechanisms.