Tipping the Scale Towards Gastric Disease: a Host-Pathogen Genomic Mismatch?

Tavera, Gloria; Morgan, Douglas R.; Williams, Scott M.

doi:10.1007/s40142-018-0153-x

Cited by 8 publications

(8 citation statements)

References 106 publications

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“…Therefore, dissecting both genetic and environmental factors that drive or prevent these diseases, is important for developing preventative strategies ( 4 , 7 ). There is a disparity in gastric cancer in the US and globally ( 8 ). In the US, nonwhites, including Latinxs, have twice the incidence rate of whites ( 9 ).…”

Section: Introductionmentioning

confidence: 99%

Helicobacter pylori infection causes both protective and deleterious effects in human health and disease

Miller

Williams

2021

Genes Immun

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Infection with Helicobacter pylori (H. pylori) is necessary but not sufficient for the development of gastric cancer, the third leading cause of cancer death globally. H. pylori infection affects over half of people globally; however, it does not affect populations uniformly. H. pylori infection rates are declining in Western industrialized countries but are plateauing in developing and newly industrialized countries where gastric cancer is most prevalent. Despite H. pylori infection being the primary causative agent for gastric cancer, H. pylori infection can also cause other effects, detrimental or beneficial, throughout an individual’s life, with the beneficial effects often being seen in childhood and the deleterious effects in adulthood. H. pylori is an ancient bacterium and its likelihood of affecting disease or health is dependent on both human and bacterial genetics that have co-evolved over millennia. In this review, we focus on the impact of infection and its genetic bases in different populations and diseases throughout an individual’s lifespan, highlighting the benefits of individualized treatment and argue that universal eradication of H. pylori in its host may cause more harm than good for those infected with H. pylori .

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Section: Introductionmentioning

confidence: 99%

Helicobacter pylori infection causes both protective and deleterious effects in human health and disease

Miller

Williams

2021

Genes Immun

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“…CIN gastric cancers arise more often in the gastro-oesophageal junction and gastric cardia (65%). Genomically stable (GS, 19.7%) with DGC [ 23 ]. …”

Section: Gastric Carcinogenesismentioning

confidence: 99%

Pathways of Gastric Carcinogenesis, Helicobacter pylori Virulence and Interactions with Antioxidant Systems, Vitamin C and Phytochemicals

Toh

Wilson

2020

IJMS

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Helicobacter pylori is a class one carcinogen which causes chronic atrophic gastritis, gastric intestinal metaplasia, dysplasia and adenocarcinoma. The mechanisms by which H. pylori interacts with other risk and protective factors, particularly vitamin C in gastric carcinogenesis are complex. Gastric carcinogenesis includes metabolic, environmental, epigenetic, genomic, infective, inflammatory and oncogenic pathways. The molecular classification of gastric cancer subtypes has revolutionized the understanding of gastric carcinogenesis. This includes the tumour microenvironment, germline mutations, and the role of Helicobacter pylori bacteria, Epstein Barr virus and epigenetics in somatic mutations. There is evidence that ascorbic acid, phytochemicals and endogenous antioxidant systems can modify the risk of gastric cancer. Gastric juice ascorbate levels depend on dietary intake of ascorbic acid but can also be decreased by H. pylori infection, H. pylori CagA secretion, tobacco smoking, achlorhydria and chronic atrophic gastritis. Ascorbic acid may be protective against gastric cancer by its antioxidant effect in gastric cytoprotection, regenerating active vitamin E and glutathione, inhibiting endogenous N-nitrosation, reducing toxic effects of ingested nitrosodimethylamines and heterocyclic amines, and preventing H. pylori infection. The effectiveness of such cytoprotection is related to H. pylori strain virulence, particularly CagA expression. The role of vitamin C in epigenetic reprogramming in gastric cancer is still evolving. Other factors in conjunction with vitamin C also play a role in gastric carcinogenesis. Eradication of H. pylori may lead to recovery of vitamin C secretion by gastric epithelium and enable regression of premalignant gastric lesions, thereby interrupting the Correa cascade of gastric carcinogenesis.

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“…H. pylori accounts for much of the attributable risk with cagA being the principal H. pylori risk genotype, and the CagA protein as the dominant virulence factor for gastric adenocarcinoma. (10)(11)(12)(13)(14) Human germline mutations are thought to be important drivers in up to 10-15% of incident GC cases. (15) An elevated risk of GC has been associated with gene polymorphisms including those in the inflammation pathway, such as genes encoding IL-1β, TNF-α, and IL-10.…”

Section: Introductionmentioning

confidence: 99%

Ornithine Decarboxylase (ODC1) gene variant (rs2302615) is associated with gastric cancer independently of Helicobacter pylori CagA serostatus

Miller

Tavera

Domínguez³

et al. 2021

Preprint

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The primary cause of gastric cancer is chronic infection with Helicobacter pylori (H.pylori) , particularly the high-risk genotype cagA, and risk modification by human genetic variants. We studied 94 variants in 54 genes for association with gastric cancer, including rs2302615 in ornithine decarboxylase (ODC1), which may affect response to chemoprevention with the ODC inhibitor, eflornithine (difluoromethylornithine; DFMO). Our population-based, case-control study included 1366 individuals (664 gastric cancer cases and 702 controls) from Western Honduras, a high incidence region of Latin America. CagA seropositivity was strongly associated with cancer (OR = 3.6; 95% CI:2.6, 5.1). The ODC1 variant rs2302615 was associated with gastric cancer (OR = 1.36; p= 0.018) in a model adjusted for age, sex, and CagA serostatus. Two additional single nucleotide polymorphisms (SNPs) in CASP1 (rs530537) and TLR4 (rs1927914) genes were also associated with gastric cancer. The ODC1 SNP association with gastric cancer was stronger in individuals who carried the TT genotype at the associating TLR4 polymorphism, rs1927914 (OR = 1.77; p = 1.85 x 10-3). In conclusion, the ODC1 variant, rs2302615, is associated with gastric cancer and supports chemoprevention trials with DFMO, particularly in individuals homozygous for the risk allele, C, at rs2302615.

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Tipping the Scale Towards Gastric Disease: a Host-Pathogen Genomic Mismatch?

Cited by 8 publications

References 106 publications

Helicobacter pylori infection causes both protective and deleterious effects in human health and disease

Helicobacter pylori infection causes both protective and deleterious effects in human health and disease

Pathways of Gastric Carcinogenesis, Helicobacter pylori Virulence and Interactions with Antioxidant Systems, Vitamin C and Phytochemicals

Ornithine Decarboxylase (ODC1) gene variant (rs2302615) is associated with gastric cancer independently of Helicobacter pylori CagA serostatus

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